Immunoexpression of transforming growth factor-β3 (TGF-β3) and receptor III of β transforming growth factor (TGF β-RIII) in pediatric patients with complete or incomplete non-syndromic cleft palate

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"textoCompleto" => "INTRODUCTIONDuring palatogenesis, the expression of transforming growth factor β1 (TGF-β1) and TGF-β2 accelerates the merging of the palatal processes;<a class="elsevierStyleCrossRef" href="#bib0005">1</a>,<a class="elsevierStyleCrossRef" href="#bib0010">2</a> while TGF-β3, which is synthesized by mesenchymal cells, contributes to the dispersion of the epithelium of the medial edge (EME) during palatal fusion.<a class="elsevierStyleCrossRefs" href="#bib0015">3–5</a> It also regulates the interactions between epithelium and mesenchymal cells involved in the formation of the palate, skin, teeth, glands, among other organs,<a class="elsevierStyleCrossRefs" href="#bib0030">6–9</a> so that the failure of both of TGF-β as well as bone morphogenetic protein (BMP) leads to a variety of craniofacial deformities including cleft palate.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>On the other hand, the type III receptor, also called β-glycan, is distributed in epithelial and mesenchymal cells; it can bind to all isoforms of TGF-β,<a class="elsevierStyleCrossRef" href="#bib0055">11</a> which can be anchored to the membrane or secreted in a soluble form.<a class="elsevierStyleCrossRefs" href="#bib0060">12–14</a> The loss of TGFβ-RIII prevents the elongation of the palatal process and its elevation, which causes the cleft.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> This is in part because of a reduction in the expression of genes TGF-β and BMP type I receptor, causing a suppression of the signaling for TGFβ-RIII, which affects the balance of such signaling pathways for adequate tissue formation.<a class="elsevierStyleCrossRef" href="#bib0080">16</a>In some studies conducted to evaluate palotogenesis by means of immunohistochemistry in murine samples in vivo and in vitro, it was determined that the expression of TGF-β3, and TGFβ-RIII<a class="elsevierStyleCrossRef" href="#bib0085">17</a> in the palate occurs when the crests present a vertical orientation. This immunoexpression was located in epithelial cells.Epithelial distribution was preserved during the elevation of the palatal crests and destruction of the medial epithelium. After palatal fusion, we observed a low expression of TGF-β3,<a class="elsevierStyleCrossRefs" href="#bib0085">17–22</a> so that some previous studies showed inhibition of the signaling for activation of TGF-β3 in murine samples taken from the palate.<a class="elsevierStyleCrossRef" href="#bib0115">23</a>,<a class="elsevierStyleCrossRef" href="#bib0120">24</a> However, mice lacking expression of TGF-β3 showed defects in palatal fusion, so that the expression of TGF-β3 is strictly limited to the epithelium of the palatal midline before fusion.<a class="elsevierStyleCrossRefs" href="#bib0125">25–29</a>With regard to the receptor, in an experimental study in mice, it was demonstrated that the expression of TGFβ-RIII during palatogenesis occurs through the epithelium, and is located specifically in the epithelium of the edge during fusion of the palatal crests.<a class="elsevierStyleCrossRefs" href="#bib0150">30–32</a> In addition, the lack of expression of TGFβ-RIII leads to an alteration in the proliferation and induction of apoptosis, as well as endothelial affection and reduction of mesenchymal cells, which affects the development of osteoblasts.<a class="elsevierStyleCrossRef" href="#bib0165">33</a>The objective of this study was to determine the immunoexpression of TGF-β3 and TGFβ-RIII in a sample of tissue from the cleft of child patients with complete or incomplete non-syndromic cleft palate, not treated with palatoplasty.Prior to taking the sample, the informed consent was signed by the parents or guardians of each patient and the process of obtaining the sample was approved by the Research Ethics Committee of the General Hospital «Dr. Manuel Gea González».MATERIAL AND METHODSSample selectionThe sample consisted of 18 patients who had complete cleft palate and two patients with incomplete cleft palate; both were non-syndromic. Eight patients were female and 12 male, from five to 28 months of age, all of them scheduled for palatoplasty for the first time.During the study we proceeded to collect a sample of tissue at the surgical procedure, which was obtained by the plastic surgeon in charge, who provided the tissue without involving an additional risk for the health of the patients.The tissue was taken from the palatal mucosa at the site of the cleft, with a size of 0.3 to 0.5 cm. The samples were fixed with formalin in a phosphate buffer solution at 10% (MEYER) and stored at 4 oC for 8 hours. Afterwards, they were placed in a PBS solution.Preparation of the immunohistochemistry for TGF-β3 and TGFβ-RIIIHistological sections were performed for each sample, of 3μ each, with their respective control. The TGF-β3 antibody was previously tested in samples of small intestine (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>), while the antibody for TGFβ-RIII was tested previously in samples of the HepG2 cell line (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>), and human being pancreas.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>The tissue samples were left to dry and de-paraffin at 60 oC overnight. Immunohistochemistry was performed in a VENTANA BenchMark Ultra machine.For the TGFβ-RIII primary monoclonal antibody (ab78421, abcam), the UltraView detection system was used (Reference 760-500, LOT E06611, expiration date 20-09-2016). The option of de-waxing at 72 oC was selected, cellular conditioning (CC1) was conducted for 20 minutes and the primary antibody was incubated 20 minutes at 36 oC.For the TGF-β3 polyclonal antibody (SC-82, Santa Cruz Biotechnology, Inc.), an OptiView detection system (Reference 760-700, Lot F08259, expiration date 28-10-2017) was used. The option of de-waxing at 72 oC was chosen with cell conditioning (CC1) for 16 minutes. The antibody was incubated for 12 minutes at 36 oC.Evaluation of the expression of TGF-β3 and TGFβ-RIII by immunohistochemistryTissue observation was performed with a binocular microscope (Axio Lab. A1). The images were taken with a ZEISS Axiocam ERc 5s camera.Monitoring and evaluation was performed by an expert pathologist who assessed the presence or absence of expression of TGF-β3 and TGFβ-RIII in the samples through the overall impression of the cells that were stained at different areas of the evaluated cleft tissue.Statistical analysisThe information was analyzed using the SPSS v20.0 statistical package. Descriptive statistics was used. For qualitative variables, percentages were used and for quantitative variables, central tendency and dispersion measurements were used.χ2 test was performed for nominal variables to compare the expression of TGF-β3 and TGFβ-RIII with complete or incomplete cleft palate.The level of significance was established at p < 0.05.RESULTSIn this study, male patients corresponded to 60% (<a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>) of the sample with an average of 13.00 ± 5.93 months of age (<a class="elsevierStyleCrossRef" href="#tbl0005">Table I</a>); whereas the female patients corresponded to 40% (<a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>), with an average of 14.25 ± 5.44 months of age (<a class="elsevierStyleCrossRef" href="#tbl0005">Table I</a>). Ninety percent of the cases had a complete cleft palate and 10%, incomplete cleft palate (<a class="elsevierStyleCrossRef" href="#fig0020">Figure 4</a>).<elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia>The patients came from the States of Mexico (40%), Mexico City (40%), Guerrero (10%), Guanajuato (5%) and Oaxaca (5%) (<a class="elsevierStyleCrossRef" href="#fig0025">Figure 5</a>).<elsevierMultimedia ident="fig0025"></elsevierMultimedia>The extent of the cleft palate was 8 to 16 mm (<a class="elsevierStyleCrossRef" href="#fig0030">Figure 6</a>), the mean for male patients was 11.66 ± 1.96 mm and in female patients of 11.37 ± 3.20 mm (<a class="elsevierStyleCrossRef" href="#tbl0010">Table II</a>).<elsevierMultimedia ident="fig0030"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>A bigger cleft size was observed in the samples of complete cleft palate (11.83 ± 2.40), than in incomplete cleft palate (9.00 ± 1.41).When comparing the frequency with which TGF-β3 and TGFβ-RIII were expressed, the following information was found:A higher positive expression of TGF-β3 was observed in the membrane and cytoplasm of epithelial cells than in the membrane and cytoplasm of fibroblasts in samples of complete and incomplete cleft palate (<a class="elsevierStyleCrossRef" href="#tbl0015">Table III</a>and<a class="elsevierStyleCrossRef" href="#fig0035">Figures 7</a>and<a class="elsevierStyleCrossRef" href="#fig0040">8</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0035"></elsevierMultimedia><elsevierMultimedia ident="fig0040"></elsevierMultimedia>In regard to TGFβ-RIII, we observed a higher positive expression in the membrane and cytoplasm of fibroblasts than in the membrane and cytoplasm of epithelial cells in complete cleft palate. In samples of incomplete cleft palate, there was a negative staining for TGFβ-RIII (<a class="elsevierStyleCrossRef" href="#tbl0015">Table III</a>and<a class="elsevierStyleCrossRef" href="#fig0045">Figure 9</a>).<elsevierMultimedia ident="fig0045"></elsevierMultimedia>When performing the χ2 test, a p = 0.008* was observed in cases of complete and incomplete cleft palate, with expression of TGF-β3, which could indicate a difference between study populations in terms of type of cleft palate, and therefore, it would be important to increase the number of samples of incomplete cleft palate in subsequent studies (<a class="elsevierStyleCrossRef" href="#tbl0015">Table III</a>).DISCUSSIONThis study determined the immunoexpression of TGF-β3 and TGFβ-RIII in a tissue sample from complete and incomplete clefts of male and female patients who underwent palatoplasty at the General Hospital «Dr. Manuel Gea González». This expression was evaluated by means of immunohistochemistry in the membrane and cytoplasm of epithelial cells and fibroblasts of the cleft palate tissue in patients within the first three years of age. This study represents one of the first performed in humans after the embryonic period. When comparing age between genders, no significant differences were found, due to the selection protocol to perform the cleft palate surgery conducted by the Department of Plastic and Reconstructive Surgery.On the other hand, more samples from patients with complete cleft were assessed in comparison with those from incomplete cleft patients. Besides, there was no significant difference in cleft width between female and male patients. This was probably due to the fact that patients received presurgical orthopaedic treatment prior to the palatoplasty.During the evaluation of TGF-β3 samples in cleft palate, positive expression was observed in all epithelial cells, which is consistent with the data observed in murine samples.<a class="elsevierStyleCrossRefs" href="#bib0085">17–22</a>In addition to squamous epithelium corresponding to the palate, epithelium of the respiratory type was detected due to the pathological anatomy resulting from the lack of fusion of the palatine crests, which allows the connection between the oral and nasal cavity.<a class="elsevierStyleCrossRef" href="#bib0170">34</a>It was noted that the squamous and respiratory epithelium was positive in the majority of cases with complete cleft palate, which is consistent with what was previously reported in humans, indicating that moderate expression of TGF-β3 has been detected in respiratory epithelium cells.<a class="elsevierStyleCrossRef" href="#bib0175">35</a>The comparison of the expression between cases of complete and incomplete cleft palate was not adequate from the statistical point of view, however, when observing the expression of TGF-β3 in the cytoplasmEste documentoof completees elaboradoandporincompleteMedigraphiccleft palate epithelial cells, there was a trend toward an increased positive expression of TGF-β3 in the epithelium of complete cleft palate.On the other hand, upon evaluation of TGFβ-RIII expression in epithelial cells of complete and incomplete cleft palate, there was a trend toward a lower positive expression in epithelium when compared with the expression of TGF-β3. This finding differs from those of previous studies,<a class="elsevierStyleCrossRefs" href="#bib0150">30–32</a> in which it was showed that the expression of TGFβ-RIII during palatogenesis occurred in the epithelium.This difference between our data and those reported in the literature, might suggest that there is a failure in signaling during inhibition or reduction of the expression of TGFβ-RIII in epithelial cells.However, the expression of TGF-β3 and TGFβ-RIII in fibroblasts, showed no differences.On the other hand, this study does not coincide with those performed on murine samples, because in spite of both being mammals species,<a class="elsevierStyleCrossRef" href="#bib0180">36</a> in humans it is observed in the majority of cases a positive inmunoexpresion; while in murine samples the absence of inmunoexpresion of both TGFβ3 and TGFβ-RIII<a class="elsevierStyleCrossRef" href="#bib0080">16</a>,<a class="elsevierStyleCrossRef" href="#bib0115">23</a>,<a class="elsevierStyleCrossRef" href="#bib0120">24</a>,<a class="elsevierStyleCrossRef" href="#bib0185">37</a> has been detected. This could be due to the difference in pathophysiology between human and mouse.In addition to the abovementioned, the expression of TGF-β3 and TGFβ-RIII could be related to the patient's age, so age might represent another variation in the results found in mice. It would be necessary to assess the expression of TGFβ3 and TGFβ-RIII in control samples of healthy patients, from 0 to 3 years of age.In subsequent studies it would be interesting to explore the differences between these types of cleft palate and cells that express TGF-β3 and TGFβ-RIII therefore it would be necessary to increase the number of samples of incomplete cleft palate.The results of the present study are all related to what has been previously reported for the placement of grafts in patients with palatal fissures because by using platelet-rich plasma, at the time of clot formation, they might release platelet-derived growth factors such as the vascular endothelial growth factor, type β transforming growth factor, epidermal growth factor, fibroblast growth factor, among others, which would induce the expression of TGFβ-RIII at epithelial level<a class="elsevierStyleCrossRefs" href="#bib0190">38–40</a> and thus strengthen the bone graft, so this is one more reason to increase research on the subject.CONCLUSIONSAfter performing the immunohistochemistry of TGFβ3 and TGFβ-RIII, it was concluded that the absence of expression of TGFβ-RIII in the epithelium of complete and incomplete cleft palate, could be related to the lack of fusion of the palatine ridges.It would be of great interest to continue to analyze in greater depth their expression in more and different cell populations besides fibroblasts and epithelial cells." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres976410" "titulo" => "ABSTRACT" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Material and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec946080" "titulo" => "Key words" ] 2 => array:3 [ "identificador" => "xres976411" "titulo" => "RESUMEN" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Material y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec946081" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "INTRODUCTION" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "MATERIAL AND METHODS" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Sample selection" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Preparation of the immunohistochemistry for TGF-β3 and TGFβ-RIII" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Evaluation of the expression of TGF-β3 and TGFβ-RIII by immunohistochemistry" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "RESULTS" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "DISCUSSION" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "CONCLUSIONS" ] 9 => array:2 [ "identificador" => "xack331213" "titulo" => "ACKNOWLEDGEMENTS" ] 10 => array:1 [ "titulo" => "REFERENCES" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec946080" "palabras" => array:3 [ 0 => "Cleft palate" 1 => "transforming growth factor β3" 2 => "receptor III of transforming growth factor β" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec946081" "palabras" => array:3 [ 0 => "Paladar hendido" 1 => "factor de crecimiento transformante-β3" 2 => "receptor III del factor de crecimiento transformante-β" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "ABSTRACT" "resumen" => "IntroductionTransforming growth factor β3 (TGF-β3), and receptor III of transforming growth factor β (TGFβ-RIII), regulate epithelial mesenchymal interactions. The lack of TGF-β3 and TGFβ-RIII expression causes defects in palatal fusion. ObjectiveTo observe the immunoexpression of TGF-β3 and TGFβ-RIII in pediatric patients with non-syndromic complete or incomplete cleft palate (CP). Material and methodsThe study design was observational, descriptive, prospective and transversal. Samples were taken from 20 complete and incomplete CP patients from five to 28 months of age. Samples of mucoperiostium were removed from the cleft in the palate during palatoplasty. In order to perform immunohistochemistry, samples were processed with VENTANA BenchMark Ultra equipment, using TGF-β3 and TGFβ-RIII antibody. Immunoexpression was evaluated by means of global cell impression. ResultsTGF-β3 immunoexpression was greater in epithelial cells than in fibroblasts of patients with complete and incomplete CP; however, TGFβ-RIII immunoexpression was greater within the fibroblasts than in epithelial cells of patients with complete cleft palate. ConclusionsIt was concluded that the lack of TGFβ-RIII expression in the epithelium may be related to the lack of fusion of the palatal shelves. It would be of great interest to perform a more in-depth analysis of the expressions of TGF-β3 and TGFβ-RIII within different cell populations." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Material and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "RESUMEN" "resumen" => "IntroducciónEl factor de crecimiento transformante β3 (TGF-β3) y el receptor III del factor de crecimiento transformante β (TGFβ-RIII), regulan las interacciones epitelio-mesenquimales. La falta de expresión de TGF-β3 y del TGF-βRIII provoca defectos en la fusión palatina. ObjetivoObservar la inmunoexpresión del TGF-β3 y del TGF-βRIII en pacientes pediátricos con paladar hendido (PH), completo o incompleto no sindrómico. Material y métodosEl diseño de estudio fue observacional, descriptivo, prospectivo y transversal. La muestra consistió de 20 pacientes con PH completo e incompleto, de cinco a 28 meses de edad. Se tomaron muestras del mucoperiostio de la hendidura palatina durante la palatoplastia. Para realizar la inmunohistoquímica, las muestras se procesaron en un aparato VENTANA BenchMark Ultra, con el anticuerpo TGF-β3 y TGFβ-RIII. Se valoró su expresión, mediante impresión global celular. ResultadosLa inmunoexpresión del TGF-β3 fue mayor en las células epiteliales que en los fibroblastos de pacientes con PH completo e incompleto; sin embargo, la inmunoexpresión del TGFβ-RIII fue mayor en los fibroblastos que en células epiteliales de pacientes con paladar hendido completo. ConclusionesSe concluyó que la falta de expresión del TGFβ-RIII en epitelio, podría tener relación con la falta de fusión de las crestas palatinas. Sería de gran interés realizar un análisis más profundo de la expresión de TGF-β3 y TGFβ-RIII, en distintas poblaciones celulares." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Material y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:8 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "This article can be read in its full version in the following page: http://www.medigraphic.com/ortodoncia" ] 1 => array:3 [ "etiqueta" => "1" "nota" => "Resident of the Division of Orthodontics and Pediatric Dentistry, General Hospital «Dr. Manuel Gea González»" "identificador" => "fn1" ] 2 => array:3 [ "etiqueta" => "2" "nota" => "Deputy Director of Pathology and in Charge of the Department of Molecular Pathology and Immunohistopathology of the National Institute of Oncology" "identificador" => "fn2" ] 3 => array:3 [ "etiqueta" => "3" "nota" => "Orthodontics visiting Professor at General Hospital «Dr. Manuel Gea González». Professor at the Metropolitan Autonomous University" "identificador" => "fn3" ] 4 => array:3 [ "etiqueta" => "4" "nota" => "Professor from the Division of Orthodontics and Pediatric Dentistry at General Hospital «Dr. Manuel Gea González»" "identificador" => "fn4" ] 5 => array:3 [ "etiqueta" => "5" "nota" => "Senior Researcher, S N I 2, Institute of Cellular Physiology, UNAM" "identificador" => "fn5" ] 6 => array:3 [ "etiqueta" => "6" "nota" => "Physician at the Division of Plastic and Reconstructive Surgery of the General Hospital «Dr. Manuel Gea González»" "identificador" => "fn6" ] 7 => array:3 [ "etiqueta" => "7" "nota" => "Professor of Research Methodology, Biostatistics, Thesis Seminar. BRIMEX Hospital ABC" "identificador" => "fn7" ] ] "multimedia" => array:12 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 594 "Ancho" => 799 "Tamanyo" => 108783 ] ] "descripcion" => array:1 [ "en" => "Positive control for immunohistochemistry of TGF-β3 in the small intestine (400x)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 600 "Ancho" => 802 "Tamanyo" => 70588 ] ] "descripcion" => array:1 [ "en" => "Positive control for immunohistochemistry of TGFβ-RIII in HepG2 cell line (400x)." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 725 "Ancho" => 1001 "Tamanyo" => 44278 ] ] "descripcion" => array:1 [ "en" => "Percentage of female and male patients." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 807 "Ancho" => 1003 "Tamanyo" => 46858 ] ] "descripcion" => array:1 [ "en" => "Percentage of patients with complete and incomplete cleft palate." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 936 "Ancho" => 663 "Tamanyo" => 59060 ] ] "descripcion" => array:1 [ "en" => "Percentage of patients according to their place of residence." ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 767 "Ancho" => 1003 "Tamanyo" => 58493 ] ] "descripcion" => array:1 [ "en" => "Palatal fissure size (mm)." ] ] 6 => array:7 [ "identificador" => "fig0035" "etiqueta" => "Figure 7" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr7.jpeg" "Alto" => 595 "Ancho" => 795 "Tamanyo" => 90147 ] ] "descripcion" => array:1 [ "en" => "Positive immunoexpression of TGF-β3 in epithelial cells from a patient with complete cleft palate (400x)." ] ] 7 => array:7 [ "identificador" => "fig0040" "etiqueta" => "Figure 8" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr8.jpeg" "Alto" => 603 "Ancho" => 792 "Tamanyo" => 110953 ] ] "descripcion" => array:1 [ "en" => "Positive immunoexpression of TGFβ-RIII, in fibroblasts of a patient with cleft palate (400x)." ] ] 8 => array:7 [ "identificador" => "fig0045" "etiqueta" => "Figure 9" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr9.jpeg" "Alto" => 594 "Ancho" => 793 "Tamanyo" => 68248 ] ] "descripcion" => array:1 [ "en" => "Absent immunoexpression of TGFβ-RIII in epitelial cells of a patient with complete cleft palate (100x)." ] ] 9 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table I" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gender \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mean \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Median \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mode \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Standard deviation \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">13.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">12.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">12.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">5.93 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">14.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">11.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">11.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">5.44 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1653594.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Age by gender expressed in months." ] ] 10 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table II" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table I" "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gender \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mean \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Median \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Mode \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Standard deviation \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">11.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">11.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">11.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">1.96 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">11.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">11.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">8.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">3.20 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1653593.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Measurement of the palatal fissure by gender." ] ] 11 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table III" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table II" "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " rowspan="2" align="center" valign="bottom" scope="col" style="border-bottom: 2px solid black">Antibody</th><th class="td" title="table-head " rowspan="2" align="center" valign="bottom" scope="col" style="border-bottom: 2px solid black">Location</th><th class="td" title="table-head " colspan="3" align="center" valign="bottom" scope="col">Immunoexpression complete cleft palate</th><th class="td" title="table-head " colspan="3" align="center" valign="bottom" scope="col">Immunoexpression incomplete cleft palate</th><th class="td" title="table-head " rowspan="2" align="center" valign="bottom" scope="col" style="border-bottom: 2px solid black">p</th></tr><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Positive(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Negative(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">NA(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Positive(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Negative(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">NA(%) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">TGF-β3</td><td class="td" title="table-entry " align="left" valign="bottom">Epithelium \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="bottom">88.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="bottom">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="bottom">11.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="center" valign="bottom">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="center" valign="bottom">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="bottom">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="bottom">0.008* \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fibroblastos \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">72.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">16.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="bottom">11.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="center" valign="bottom">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="center" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">0.119 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">TGFβ-RIII</td><td class="td" title="table-entry " align="left" valign="top">Epithelium \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">44.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">33.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="bottom">22.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="center" valign="bottom">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="center" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="top">0.452 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="bottom">Fibroblasts \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="bottom">72.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="bottom">16.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="bottom">11.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="center" valign="bottom">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="center" valign="bottom">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="bottom">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="right" valign="bottom">0.119 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1653595.png" ] ] ] ] "descripcion" => array:1 [ "en" => "*χ2 test. Expression of TGF-β3 and TGFβ-RIII in epithelial cells and fibroblasts of complete and incomplete cleft palate. A higher positive expression of TGF-β3, was observed in epithelium and more positive expression of TGFβ-RIII in fibroblasts." ] ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:40 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effects of epidermal growth factor, transforming growth factors alpha and beta and platelet-derived growth factor on murine palatal shelves in organ culture" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.J. Dixon" 1 => "M.W. Ferguson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Arch Oral Biol." 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"fecha" => "2011" "volumen" => "56" "numero" => "2" "paginaInicial" => "63" "paginaFinal" => "75" ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack331213" "titulo" => "ACKNOWLEDGEMENTS" "texto" => "To all the staff of the Division of Stomatology-Orthodontics and the Division of Plastic and Reconstructive Surgery, General Hospital «Dr. Manuel Gea González» who facilitated the collection of samples. To the staff of the Department of Molecular Pathology and Immunohistopathology of the National Institute of Cancerology for all their contributions, availability, and lessons learned during the project. Mainly I would like to thank Q.F.B. Guadalupe Moncada Claudio, and Q.F.B. Maria de Lourdes Peña Torres for their great assistance for the realization of the immunohistochemistry. I also thank the Institute of Cellular Physiology, UNAM, mainly M.S. Tonatiuh Molina Villa for his contribution and support for the realization of cell cultures, which are indispensable for the achievement of the controls." "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/23959215/0000000500000004/v1_201802071836/S2395921518300126/v1_201802071836/en/main.assets" "Apartado" => array:4 [ "identificador" => "59223" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original research" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23959215/0000000500000004/v1_201802071836/S2395921518300126/v1_201802071836/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2395921518300126?idApp=UINPBA00004N"]

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Inmunoexpresión del factor de crecimiento transformante β3 (TGF-β3) y del receptor III del factor de crecimiento transformante β (TGF β-RIII) en pacientes pediátricos con paladar hendido completo o incompleto no sindromático

Carolina López González1,

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caroleta21@hotmail.com

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, Héctor Aquiles Maldonado Martínez2, Salvador García López3, María del Carmen Rosas Ramírez4, Fernando López Casillas5, Araceli Pérez González6, Dulce Haydeé Gutiérrez Valdez7

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skin&#44; teeth&#44; glands&#44; among other organs&#44;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;9</span></a> so that the failure of both of TGF-&#946; as well as bone morphogenetic protein &#40;BMP&#41; leads to a variety of craniofacial deformities including cleft palate&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">On the other hand&#44; the type III receptor&#44; also called &#946;-glycan&#44; is distributed in epithelial and mesenchymal cells&#59; it can bind to all isoforms of TGF-&#946;&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> which can be anchored to the membrane or secreted in a soluble form&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#8211;14</span></a> The loss of TGF&#946;-RIII prevents the elongation of the palatal process and its elevation&#44; which causes the cleft&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> This is in part because of a reduction in the expression of genes TGF-&#946; and BMP type I receptor&#44; causing a suppression of the signaling for TGF&#946;-RIII&#44; which affects the balance of such signaling pathways for adequate tissue formation&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In some studies conducted to evaluate palotogenesis by means of immunohistochemistry in murine samples <span class="elsevierStyleItalic">in vivo</span> and <span class="elsevierStyleItalic">in vitro</span>&#44; it was determined that the expression of TGF-&#946;3&#44; and TGF&#946;-RIII<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> in the palate occurs when the crests present a vertical orientation&#46; This immunoexpression was located in epithelial cells&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Epithelial distribution was preserved during the elevation of the palatal crests and destruction of the medial epithelium&#46; 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and is located specifically in the epithelium of the edge during fusion of the palatal crests&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#8211;32</span></a> In addition&#44; the lack of expression of TGF&#946;-RIII leads to an alteration in the proliferation and induction of apoptosis&#44; as well as endothelial affection and reduction of mesenchymal cells&#44; which affects the development of osteoblasts&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The objective of this study was to determine the immunoexpression of TGF-&#946;3 and TGF&#946;-RIII in a sample of tissue from the cleft of child patients with complete or incomplete non-syndromic cleft palate&#44; not treated with palatoplasty&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Prior to taking the sample&#44; the informed consent was signed by the parents or guardians of each patient and the process of obtaining the sample was approved by the Research Ethics Committee of the General Hospital &#171;Dr&#46; Manuel Gea Gonz&#225;lez&#187;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">MATERIAL AND METHODS</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Sample selection</span><p id="par0040" class="elsevierStylePara elsevierViewall">The sample consisted of 18 patients who had complete cleft palate and two patients with incomplete cleft palate&#59; both were non-syndromic&#46; Eight patients were female and 12 male&#44; from five to 28 months of age&#44; all of them scheduled for palatoplasty for the first time&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">During the study we proceeded to collect a sample of tissue at the surgical procedure&#44; which was obtained by the plastic surgeon in charge&#44; who provided the tissue without involving an additional risk for the health of the patients&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The tissue was taken from the palatal mucosa at the site of the cleft&#44; with a size of 0&#46;3 to 0&#46;5 cm&#46; The samples were fixed with formalin in a phosphate buffer solution at 10&#37; &#40;MEYER&#41; and stored at 4 <span class="elsevierStyleSup">o</span>C for 8 hours&#46; Afterwards&#44; they were placed in a PBS solution&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Preparation of the immunohistochemistry for TGF-&#946;3 and TGF&#946;-RIII</span><p id="par0055" class="elsevierStylePara elsevierViewall">Histological sections were performed for each sample&#44; of 3&#956; each&#44; with their respective control&#46; The TGF-&#946;3 antibody was previously tested in samples of small intestine <span class="elsevierStyleItalic">&#40;</span><a class="elsevierStyleCrossRef" href="#fig0005"><span class="elsevierStyleItalic">Figure 1</span></a><span class="elsevierStyleItalic">&#41;</span>&#44; while the antibody for TGF&#946;-RIII was tested previously in samples of the HepG2 cell line <span class="elsevierStyleItalic">&#40;</span><a class="elsevierStyleCrossRef" href="#fig0010"><span class="elsevierStyleItalic">Figure 2</span></a><span class="elsevierStyleItalic">&#41;</span>&#44; and human being pancreas&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">The tissue samples were left to dry and de-paraffin at 60 <span class="elsevierStyleSup">o</span>C overnight&#46; Immunohistochemistry was performed in a VENTANA BenchMark Ultra machine&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">For the TGF&#946;-RIII primary monoclonal antibody &#40;ab78421&#44; abcam&#41;&#44; the UltraView detection system was used &#40;Reference 760-500&#44; LOT E06611&#44; expiration date 20-09-2016&#41;&#46; The option of de-waxing at 72 <span class="elsevierStyleSup">o</span>C was selected&#44; cellular conditioning &#40;CC1&#41; was conducted for 20 minutes and the primary antibody was incubated 20 minutes at 36 <span class="elsevierStyleSup">o</span>C&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">For the TGF-&#946;3 polyclonal antibody &#40;SC-82&#44; Santa Cruz Biotechnology&#44; Inc&#46;&#41;&#44; an OptiView detection system &#40;Reference 760-700&#44; Lot F08259&#44; expiration date 28-10-2017&#41; was used&#46; The option of de-waxing at 72 <span class="elsevierStyleSup">o</span>C was chosen with cell conditioning &#40;CC1&#41; for 16 minutes&#46; The antibody was incubated for 12 minutes at 36 <span class="elsevierStyleSup">o</span>C&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Evaluation of the expression of TGF-&#946;3 and TGF&#946;-RIII by immunohistochemistry</span><p id="par0075" class="elsevierStylePara elsevierViewall">Tissue observation was performed with a binocular microscope &#40;Axio Lab&#46; A1&#41;&#46; The images were taken with a ZEISS Axiocam ERc 5s camera&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Monitoring and evaluation was performed by an expert pathologist who assessed the presence or absence of expression of TGF-&#946;3 and TGF&#946;-RIII in the samples through the overall impression of the cells that were stained at different areas of the evaluated cleft tissue&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0085" class="elsevierStylePara elsevierViewall">The information was analyzed using the SPSS v20&#46;0 statistical package&#46; Descriptive statistics was used&#46; For qualitative variables&#44; percentages were used and for quantitative variables&#44; central tendency and dispersion measurements were used&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">&#967;<span class="elsevierStyleSup">2</span> test was performed for nominal variables to compare the expression of TGF-&#946;3 and TGF&#946;-RIII with complete or incomplete cleft palate&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The level of significance was established at p &#60; 0&#46;05&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">RESULTS</span><p id="par0100" class="elsevierStylePara elsevierViewall">In this study&#44; male patients corresponded to 60&#37; <span class="elsevierStyleItalic">&#40;</span><a class="elsevierStyleCrossRef" href="#fig0015"><span class="elsevierStyleItalic">Figure 3</span></a><span class="elsevierStyleItalic">&#41;</span> of the sample with an average of 13&#46;00 &#177; 5&#46;93 months of age <span class="elsevierStyleItalic">&#40;</span><a class="elsevierStyleCrossRef" href="#tbl0005"><span class="elsevierStyleItalic">Table I</span></a><span class="elsevierStyleItalic">&#41;</span>&#59; whereas the female patients corresponded to 40&#37; <span class="elsevierStyleItalic">&#40;</span><a class="elsevierStyleCrossRef" href="#fig0015"><span class="elsevierStyleItalic">Figure 3</span></a><span class="elsevierStyleItalic">&#41;</span>&#44; with an average of 14&#46;25 &#177; 5&#46;44 months of age <span class="elsevierStyleItalic">&#40;</span><a class="elsevierStyleCrossRef" href="#tbl0005"><span class="elsevierStyleItalic">Table I</span></a><span class="elsevierStyleItalic">&#41;</span>&#46; Ninety percent of the cases had a complete cleft palate and 10&#37;&#44; incomplete cleft palate <span class="elsevierStyleItalic">&#40;</span><a class="elsevierStyleCrossRef" href="#fig0020"><span class="elsevierStyleItalic">Figure 4</span></a><span class="elsevierStyleItalic">&#41;</span>&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">The patients came from the States of Mexico &#40;40&#37;&#41;&#44; Mexico City &#40;40&#37;&#41;&#44; Guerrero &#40;10&#37;&#41;&#44; Guanajuato &#40;5&#37;&#41; and Oaxaca &#40;5&#37;&#41; <span class="elsevierStyleItalic">&#40;</span><a class="elsevierStyleCrossRef" href="#fig0025"><span class="elsevierStyleItalic">Figure 5</span></a><span class="elsevierStyleItalic">&#41;</span>&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">The extent of the cleft palate was 8 to 16 mm <span class="elsevierStyleItalic">&#40;</span><a class="elsevierStyleCrossRef" href="#fig0030"><span class="elsevierStyleItalic">Figure 6</span></a><span class="elsevierStyleItalic">&#41;</span>&#44; the mean for male patients was 11&#46;66 &#177; 1&#46;96 mm and in female patients of 11&#46;37 &#177; 3&#46;20 mm <span class="elsevierStyleItalic">&#40;</span><a class="elsevierStyleCrossRef" href="#tbl0010"><span class="elsevierStyleItalic">Table II</span></a><span class="elsevierStyleItalic">&#41;</span>&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">A bigger cleft size was observed in the samples of complete cleft palate &#40;11&#46;83 &#177; 2&#46;40&#41;&#44; than in incomplete cleft palate &#40;9&#46;00 &#177; 1&#46;41&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">When comparing the frequency with which TGF-&#946;3 and TGF&#946;-RIII were expressed&#44; the following information was found&#58;</p><p id="par0125" class="elsevierStylePara elsevierViewall">A higher positive expression of TGF-&#946;3 was observed in the membrane and cytoplasm of epithelial cells than in the membrane and cytoplasm of fibroblasts in samples of complete and incomplete cleft palate <span class="elsevierStyleItalic">&#40;</span><a class="elsevierStyleCrossRef" href="#tbl0015"><span class="elsevierStyleItalic">Table III</span></a><span class="elsevierStyleItalic">and</span><a class="elsevierStyleCrossRef" href="#fig0035"><span class="elsevierStyleItalic">Figures 7</span></a><span class="elsevierStyleItalic">and</span><a class="elsevierStyleCrossRef" href="#fig0040"><span class="elsevierStyleItalic">8</span></a><span class="elsevierStyleItalic">&#41;</span>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0035"></elsevierMultimedia><elsevierMultimedia ident="fig0040"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">In regard to TGF&#946;-RIII&#44; we observed a higher positive expression in the membrane and cytoplasm of fibroblasts than in the membrane and cytoplasm of epithelial cells in complete cleft palate&#46; In samples of incomplete cleft palate&#44; there was a negative staining for TGF&#946;-RIII <span class="elsevierStyleItalic">&#40;</span><a class="elsevierStyleCrossRef" href="#tbl0015"><span class="elsevierStyleItalic">Table III</span></a><span class="elsevierStyleItalic">and</span><a class="elsevierStyleCrossRef" href="#fig0045"><span class="elsevierStyleItalic">Figure 9</span></a><span class="elsevierStyleItalic">&#41;</span>&#46;</p><elsevierMultimedia ident="fig0045"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">When performing the &#967;<span class="elsevierStyleSup">2</span> test&#44; a p &#61; 0&#46;008&#42; was observed in cases of complete and incomplete cleft palate&#44; with expression of TGF-&#946;3&#44; which could indicate a difference between study populations in terms of type of cleft palate&#44; and therefore&#44; it would be important to increase the number of samples of incomplete cleft palate in subsequent studies <span class="elsevierStyleItalic">&#40;</span><a class="elsevierStyleCrossRef" href="#tbl0015"><span class="elsevierStyleItalic">Table III</span></a><span class="elsevierStyleItalic">&#41;</span>&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">DISCUSSION</span><p id="par0140" class="elsevierStylePara elsevierViewall">This study determined the immunoexpression of TGF-&#946;3 and TGF&#946;-RIII in a tissue sample from complete and incomplete clefts of male and female patients who underwent palatoplasty at the General Hospital &#171;Dr&#46; Manuel Gea Gonz&#225;lez&#187;&#46; This expression was evaluated by means of immunohistochemistry in the membrane and cytoplasm of epithelial cells and fibroblasts of the cleft palate tissue in patients within the first three years of age&#46; This study represents one of the first performed in humans after the embryonic period&#46; When comparing age between genders&#44; no significant differences were found&#44; due to the selection protocol to perform the cleft palate surgery conducted by the Department of Plastic and Reconstructive Surgery&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">On the other hand&#44; more samples from patients with complete cleft were assessed in comparison with those from incomplete cleft patients&#46; Besides&#44; there was no significant difference in cleft width between female and male patients&#46; This was probably due to the fact that patients received presurgical orthopaedic treatment prior to the palatoplasty&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">During the evaluation of TGF-&#946;3 samples in cleft palate&#44; positive expression was observed in all epithelial cells&#44; which is consistent with the data observed in murine samples&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#8211;22</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">In addition to squamous epithelium corresponding to the palate&#44; epithelium of the respiratory type was detected due to the pathological anatomy resulting from the lack of fusion of the palatine crests&#44; which allows the connection between the oral and nasal cavity&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">It was noted that the squamous and respiratory epithelium was positive in the majority of cases with complete cleft palate&#44; which is consistent with what was previously reported in humans&#44; indicating that moderate expression of TGF-&#946;3 has been detected in respiratory epithelium cells&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">The comparison of the expression between cases of complete and incomplete cleft palate was not adequate from the statistical point of view&#44; however&#44; when observing the expression of TGF-&#946;3 in the cytoplasmEste documentoof completees elaboradoandporincompleteMedigraphiccleft palate epithelial cells&#44; there was a trend toward an increased positive expression of TGF-&#946;3 in the epithelium of complete cleft palate&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">On the other hand&#44; upon evaluation of TGF&#946;-RIII expression in epithelial cells of complete and incomplete cleft palate&#44; there was a trend toward a lower positive expression in epithelium when compared with the expression of TGF-&#946;3&#46; This finding differs from those of previous studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#8211;32</span></a> in which it was showed that the expression of TGF&#946;-RIII during palatogenesis occurred in the epithelium&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">This difference between our data and those reported in the literature&#44; might suggest that there is a failure in signaling during inhibition or reduction of the expression of TGF&#946;-RIII in epithelial cells&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">However&#44; the expression of TGF-&#946;3 and TGF&#946;-RIII in fibroblasts&#44; showed no differences&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">On the other hand&#44; this study does not coincide with those performed on murine samples&#44; because in spite of both being mammals species&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> in humans it is observed in the majority of cases a positive inmunoexpresion&#59; while in murine samples the absence of inmunoexpresion of both TGF&#946;3 and TGF&#946;-RIII<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> has been detected&#46; This could be due to the difference in pathophysiology between human and mouse&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In addition to the abovementioned&#44; the expression of TGF-&#946;3 and TGF&#946;-RIII could be related to the patient&#39;s age&#44; so age might represent another variation in the results found in mice&#46; It would be necessary to assess the expression of TGF&#946;3 and TGF&#946;-RIII in control samples of healthy patients&#44; from 0 to 3 years of age&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">In subsequent studies it would be interesting to explore the differences between these types of cleft palate and cells that express TGF-&#946;3 and TGF&#946;-RIII therefore it would be necessary to increase the number of samples of incomplete cleft palate&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">The results of the present study are all related to what has been previously reported for the placement of grafts in patients with palatal fissures because by using platelet-rich plasma&#44; at the time of clot formation&#44; they might release platelet-derived growth factors such as the vascular endothelial growth factor&#44; type &#946; transforming growth factor&#44; epidermal growth factor&#44; fibroblast growth factor&#44; among others&#44; which would induce the expression of TGF&#946;-RIII at epithelial level<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">38&#8211;40</span></a> and thus strengthen the bone graft&#44; so this is one more reason to increase research on the subject&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">CONCLUSIONS</span><p id="par0205" class="elsevierStylePara elsevierViewall">After performing the immunohistochemistry of TGF&#946;3 and TGF&#946;-RIII&#44; it was concluded that the absence of expression of TGF&#946;-RIII in the epithelium of complete and incomplete cleft palate&#44; could be related to the lack of fusion of the palatine ridges&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">It would be of great interest to continue to analyze in greater depth their expression in more and different cell populations besides fibroblasts and epithelial cells&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Transforming growth factor &#946;3 &#40;TGF-&#946;3&#41;&#44; and receptor III of transforming growth factor &#946; &#40;TGF&#946;-RIII&#41;&#44; regulate epithelial mesenchymal interactions&#46; The lack of TGF-&#946;3 and TGF&#946;-RIII expression causes defects in palatal fusion&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To observe the immunoexpression of TGF-&#946;3 and TGF&#946;-RIII in pediatric patients with non-syndromic complete or incomplete cleft palate &#40;CP&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Material and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The study design was observational&#44; descriptive&#44; prospective and transversal&#46; Samples were taken from 20 complete and incomplete CP patients from five to 28 months of age&#46; Samples of mucoperiostium were removed from the cleft in the palate during palatoplasty&#46; In order to perform immunohistochemistry&#44; samples were processed with VENTANA BenchMark Ultra equipment&#44; using TGF-&#946;3 and TGF&#946;-RIII antibody&#46; Immunoexpression was evaluated by means of global cell impression&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">TGF-&#946;3 immunoexpression was greater in epithelial cells than in fibroblasts of patients with complete and incomplete CP&#59; however&#44; TGF&#946;-RIII immunoexpression was greater within the fibroblasts than in epithelial cells of patients with complete cleft palate&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">It was concluded that the lack of TGF&#946;-RIII expression in the epithelium may be related to the lack of fusion of the palatal shelves&#46; It would be of great interest to perform a more in-depth analysis of the expressions of TGF-&#946;3 and TGF&#946;-RIII within different cell populations&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El factor de crecimiento transformante &#946;3 &#40;TGF-&#946;3&#41; y el receptor III del factor de crecimiento transformante &#946; &#40;TGF&#946;-RIII&#41;&#44; regulan las interacciones epitelio-mesenquimales&#46; La falta de expresi&#243;n de TGF-&#946;3 y del TGF-&#946;RIII provoca defectos en la fusi&#243;n palatina&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Observar la inmunoexpresi&#243;n del TGF-&#946;3 y del TGF-&#946;RIII en pacientes pedi&#225;tricos con paladar hendido &#40;PH&#41;&#44; completo o incompleto no sindr&#243;mico&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Material y m&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El dise&#241;o de estudio fue observacional&#44; descriptivo&#44; prospectivo y transversal&#46; La muestra consisti&#243; de 20 pacientes con PH completo e incompleto&#44; de cinco a 28 meses de edad&#46; Se tomaron muestras del mucoperiostio de la hendidura palatina durante la palatoplastia&#46; Para realizar la inmunohistoqu&#237;mica&#44; las muestras se procesaron en un aparato VENTANA BenchMark Ultra&#44; con el anticuerpo TGF-&#946;3 y TGF&#946;-RIII&#46; Se valor&#243; su expresi&#243;n&#44; mediante impresi&#243;n global celular&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La inmunoexpresi&#243;n del TGF-&#946;3 fue mayor en las c&#233;lulas epiteliales que en los fibroblastos de pacientes con PH completo e incompleto&#59; sin embargo&#44; la inmunoexpresi&#243;n del TGF&#946;-RIII fue mayor en los fibroblastos que en c&#233;lulas epiteliales de pacientes con paladar hendido completo&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Se concluy&#243; que la falta de expresi&#243;n del TGF&#946;-RIII en epitelio&#44; podr&#237;a tener relaci&#243;n con la falta de fusi&#243;n de las crestas palatinas&#46; Ser&#237;a de gran inter&#233;s realizar un an&#225;lisis m&#225;s profundo de la expresi&#243;n de TGF-&#946;3 y TGF&#946;-RIII&#44; en distintas poblaciones celulares&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">This article can be read in its full version in the following page&#58; <span class="elsevierStyleInterRef" id="intr0005" href="http://www.medigraphic.com/ortodoncia">http&#58;&#47;&#47;www&#46;medigraphic&#46;com&#47;ortodoncia</span></p>"
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      1 => array:3 [
        "etiqueta" => "1"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Resident of the Division of Orthodontics and Pediatric Dentistry&#44; General Hospital &#171;Dr&#46; Manuel Gea Gonz&#225;lez&#187;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Deputy Director of Pathology and in Charge of the Department of Molecular Pathology and Immunohistopathology of the National Institute of Oncology</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Orthodontics visiting Professor at General Hospital &#171;Dr&#46; Manuel Gea Gonz&#225;lez&#187;&#46; Professor at the Metropolitan Autonomous University</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Professor from the Division of Orthodontics and Pediatric Dentistry at General Hospital &#171;Dr&#46; Manuel Gea Gonz&#225;lez&#187;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0040">Professor of Research Methodology&#44; Biostatistics&#44; Thesis Seminar&#46; BRIMEX Hospital ABC</p>"
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Positive control for immunohistochemistry of TGF-&#946;3 in the small intestine &#40;400x&#41;&#46;</p>"
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Percentage of female and male patients&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gender&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mean&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="top">12&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="top">5&#46;93&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gender&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " rowspan="2" align="center" valign="bottom" scope="col" style="border-bottom: 2px solid black">Antibody</th><th class="td" title="table-head  " rowspan="2" align="center" valign="bottom" scope="col" style="border-bottom: 2px solid black">Location</th><th class="td" title="table-head  " colspan="3" align="center" valign="bottom" scope="col">Immunoexpression complete cleft palate</th><th class="td" title="table-head  " colspan="3" align="center" valign="bottom" scope="col">Immunoexpression incomplete cleft palate</th><th class="td" title="table-head  " rowspan="2" align="center" valign="bottom" scope="col" style="border-bottom: 2px solid black">p</th></tr><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Positive&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">TGF-&#946;3</td><td class="td" title="table-entry  " align="left" valign="bottom">Epithelium&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="bottom">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fibroblastos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="top">72&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="top">16&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="bottom">11&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="bottom">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="top">0&#46;119&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">TGF&#946;-RIII</td><td class="td" title="table-entry  " align="left" valign="top">Epithelium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="top">44&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="top">33&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="bottom">22&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="bottom">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="top">0&#46;452&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="bottom">Fibroblasts&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="bottom">72&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="bottom">16&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="bottom">11&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="bottom">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="bottom">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="bottom">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="right" valign="bottom">0&#46;119&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab1653595.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">&#42;&#967;<span class="elsevierStyleSup">2</span> test&#46; Expression of TGF-&#946;3 and TGF&#946;-RIII in epithelial cells and fibroblasts of complete and incomplete cleft palate&#46; A higher positive expression of TGF-&#946;3&#44; was observed in epithelium and more positive expression of TGF&#946;-RIII in fibroblasts&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
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Article information

ISSN: 23959215
Original language: English

DOI:10.1016/j.rmo.2018.01.012

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	2	0	2
2024 October	54	0	54
2024 September	74	0	74
2024 August	35	4	39
2024 July	31	0	31
2024 June	22	4	26
2024 May	20	2	22
2024 April	32	6	38
2024 March	53	1	54
2024 February	33	7	40
2024 January	109	6	115
2023 December	43	11	54
2023 November	43	11	54
2023 October	57	18	75
2023 September	47	2	49
2023 August	24	2	26
2023 July	17	3	20
2023 June	25	6	31
2023 May	35	3	38
2023 April	34	3	37
2023 March	17	3	20
2023 February	31	9	40
2023 January	20	9	29
2022 December	47	8	55
2022 November	30	14	44
2022 October	39	12	51
2022 September	22	13	35
2022 August	23	19	42
2022 July	19	5	24
2022 June	23	24	47
2022 May	22	17	39
2022 April	34	26	60
2022 March	57	17	74
2022 February	39	6	45
2022 January	30	9	39
2021 December	25	10	35
2021 November	29	11	40
2021 October	34	13	47
2021 September	33	20	53
2021 August	26	4	30
2021 July	198	12	210
2021 June	20	7	27
2021 May	32	6	38
2021 April	52	9	61
2021 March	65	13	78
2021 February	27	13	40
2021 January	22	14	36
2020 December	33	7	40
2020 November	53	10	63
2020 October	34	6	40
2020 September	38	11	49
2020 August	38	7	45
2020 July	24	10	34
2020 June	23	9	32
2020 May	38	7	45
2020 April	43	8	51
2020 March	32	9	41
2020 February	20	7	27
2020 January	26	13	39
2019 December	31	11	42
2019 November	28	8	36
2019 October	20	12	32
2019 September	25	10	35
2019 August	14	7	21
2019 July	17	7	24
2019 June	36	15	51
2019 May	58	10	68
2019 April	30	8	38
2019 March	13	3	16
2019 February	16	6	22
2019 January	16	7	23
2018 December	4	7	11
2018 November	13	8	21
2018 October	9	25	34
2018 September	10	0	10
2018 August	6	0	6
2018 July	6	1	7
2018 June	19	1	20
2018 May	12	0	12
2018 April	13	0	13
2018 March	13	0	13
2018 February	9	2	11

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