{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T04:25:58Z","timestamp":1772598358879,"version":"3.50.1"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hirschsprung disease (HD) involves aganglionosis of the intestinal segment, with unclear etiology and challenging histopathological identification. The etiology of Hirschsprung\u2212associated enterocolitis (HAEC) remains elusive. This study aims to explore the potential roles of Laminin and BCL-2 in the etiology of HD and HAEC by examining their expression levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Tissues from 20 Rectosigmoid Hirschsprung patients (10 with and 10 without postoperative HAEC) and 10 controls were analyzed retrospectively. Protein expression was analyzed using immunohistochemistry, mRNA levels were measured using Real-Time PCR, and DNA mutations were found using Sanger Sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BCL-2 immunohistochemistry indicated decreased expression in HD patients\u2019 aganglionic tissues compared to ganglionic tissues (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.001).\n                      <jats:italic>BCL-2<\/jats:italic>\n                      mRNA expression was significantly lower in HD patients\u2019 tissues than in controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Laminin immunohistochemistry revealed significant positive staining in ganglionic tissues, with most aganglionic tissues negative and some mildly positive (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.016). There was no significant association between BCL-2, Laminin, and HAEC (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05). DNA sequencing discovered a novel\n                      <jats:italic>BCL-2<\/jats:italic>\n                      gene mutation in HD patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      BCL-2 and Laminin immunohistochemistry can differentiate ganglionic and aganglionic tissues. Reduced\n                      <jats:italic>BCL-2<\/jats:italic>\n                      mRNA expression in HD patients indicates a disease that affects the whole gut. More research is needed on the new\n                      <jats:italic>BCL-2<\/jats:italic>\n                      gene mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact statement<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            This is the first study to examine the correlation between BCL-2 and Laminin expression changes and enterocolitis developing in HD. It is a previously unreported contribution to the literature that\n                            <jats:italic>BCL-2<\/jats:italic>\n                            mRNA expression was lower than expected in all intestinal tissues of HD patients, including the intestinal tissues considered to be healthy. Mutagenic changes have been detected in the\n                            <jats:italic>BCL-2<\/jats:italic>\n                            gene of some HD patients. A definitive novel mutation, which has not been reported in the literature before, was detected in one patient.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-025-03994-2","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T15:16:56Z","timestamp":1744643816000},"page":"759-766","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Expression of BCL-2 and Laminin in Rectosigmoid Hirschsprung Disease: Correlations with Hirschsprung\u2212Associated Enterocolitis"],"prefix":"10.1038","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2346-7802","authenticated-orcid":false,"given":"Merve","family":"Dede","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7960-4477","authenticated-orcid":false,"given":"Fatih","family":"Celik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2520-1856","authenticated-orcid":false,"given":"Ebrucan","family":"Bulut","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7710-7613","authenticated-orcid":false,"given":"Rumeysa Fatma","family":"Balaban","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2822-3663","authenticated-orcid":false,"given":"Nuseybe","family":"Huriyet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4913-3616","authenticated-orcid":false,"given":"Ufuk","family":"Unal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0127-548X","authenticated-orcid":false,"given":"Nesrin","family":"Ugras","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3820-424X","authenticated-orcid":false,"given":"Gulsah","family":"Cecener","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7244-6736","authenticated-orcid":false,"given":"Irfan","family":"Kiristioglu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"3994_CR1","unstructured":"Basaklar, C. 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