Gastroenterology ReportPub Date : 2026-03-27eCollection Date: 2026-02-01DOI: 10.1093/gastro/goag016
Chang Sun, Changsen Leng, Mingyue Sun, Yuan Lin, Mingqian Xu, Águeda Martinez-Barriocanal, Albert Gerding, Jeroen Kuipers, Jim de Leeuw, Barbara M Bakker, Diego Arango, Sven C D van IJzendoorn
{"title":"Microvillus inclusion disease-associated MYO5B deficiency impairs endosome-to-mitochondrion iron transfer.","authors":"Chang Sun, Changsen Leng, Mingyue Sun, Yuan Lin, Mingqian Xu, Águeda Martinez-Barriocanal, Albert Gerding, Jeroen Kuipers, Jim de Leeuw, Barbara M Bakker, Diego Arango, Sven C D van IJzendoorn","doi":"10.1093/gastro/goag016","DOIUrl":"10.1093/gastro/goag016","url":null,"abstract":"<p><strong>Background: </strong>MYO5B deficiency causes microvillus inclusion disease (MVID), characterized by the inability to absorb dietary nutrients and secretory diarrhea. MVID intestinal tissue shows metabolic abnormalities, but the causality with MYO5B and the underlying mechanism are unknown. The aim of this study was to determine the effects of MYO5B deficiency on mitochondria as key regulators of cellular metabolism and the underlying mechanism.</p><p><strong>Methods: </strong>Intestinal tissue from MVID patients and inducible intestine-specific <i>myo5b</i>-knockout (KO) mouse were examined by using light and large-scale scanning transmission electron microscopy. CRISPR-Cas9 was used to generate <i>MYO5B</i> KO intestinal Caco2 cells. Site-directed mutagenesis was performed to generate <i>MYO5B</i> mutants. Fluorescence-based indicators of mitochondrial membrane potential and iron levels, analyses of carbonylated protein residues from isolated mitochondria, and high-resolution respirometry were used to assess mitochondrial homeostasis and function.</p><p><strong>Results: </strong>MYO5B-deficient Caco2 cells showed fragmented and swollen mitochondria, reduced intra-mitochondrial cristae, defective aerobic respiration, reduced mitochondrial membrane potential, and increased mitochondrial oxidative stress. Introduction of a myc-tagged full-length MYO5B in <i>MYO5B</i> KO cells restored membrane potential, whereas the MVID-causing MYO5B-p.(Pro660Leu) variant and the MYO5B-p.(Lys1534Ala) and -p.(Leu1597Pro) mutants did not, demonstrating causality. Quantitative 3D fluorescence microscopy revealed close associations between mitochondria and MYO5B-positive endosomes carrying the iron-transporting transferrin. Associations between transferrin-loaded endosomes and mitochondria were diminished in MYO5B-depleted Caco2 cells. MYO5B-deficient Caco2 cells showed reduced mitochondrial iron content and an accumulation of iron in the endosomal system.</p><p><strong>Conclusion: </strong>MYO5B deficiency impairs endosome-to-mitochondrial iron transfer, leading to mitochondrial dysfunction. These results offer a novel therapeutic avenue aimed at restoring mitochondrial function in MVID.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"14 ","pages":"goag016"},"PeriodicalIF":4.2,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastroenterology ReportPub Date : 2026-03-23eCollection Date: 2026-02-01DOI: 10.1093/gastro/goag028
Christina Parassiadis, Steven A Johnsen
{"title":"Epigenetic and transcriptional control of classical and basal-like cell states in pancreatic ductal adenocarcinoma.","authors":"Christina Parassiadis, Steven A Johnsen","doi":"10.1093/gastro/goag028","DOIUrl":"10.1093/gastro/goag028","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a 5-year survival of only ∼13%. Despite incremental advances through combination chemotherapy, most patients relapse rapidly due to profound molecular heterogeneity and intrinsic resistance. Recent genomic and transcriptomic studies have defined distinct PDAC molecular subtypes, classical and basal-like, which differ in differentiation state, prognosis, and therapeutic vulnerability. Classical tumors, marked by GATA6 and hepatocyte nuclear factors, exhibit epithelial identity and relative chemosensitivity, whereas basal-like tumors driven by ΔNp63 and MYC display mesenchymal and inflammatory programs associated with resistance and poor outcome. Importantly, these subtypes are dynamic, with single-cell and spatial analyses revealing frequent coexistence and therapy-induced transitions, highlighting cellular plasticity as a major determinant of treatment response. Subtype identity is governed by lineage-defining transcription factors, chromatin regulators, and stromal cues that integrate to form reversible epigenetic states. Targeting these mechanisms with inhibitors of EZH2, BET proteins, or CDK9 can restore differentiation programs and resensitize tumors to chemotherapy. Integrating molecular subtyping with epigenetic modulation thus offers a rational path toward biomarker-guided therapy. Continued efforts combining spatially resolved profiling, organoid modeling, and liquid-biopsy monitoring will be essential to capture tumor evolution in real time. Understanding and therapeutically exploiting the transcriptional and epigenetic plasticity in PDAC may ultimately enable reprogramming of resistant states and improve clinical outcomes in this intractable disease.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"14 ","pages":"goag028"},"PeriodicalIF":4.2,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13006169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147516626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastroenterology ReportPub Date : 2026-03-22eCollection Date: 2026-02-01DOI: 10.1093/gastro/goag025
Jianlei Liu, Xiaochun Zhang, Xiaorui Ye, Jun Wang, Yang Yang, Jiabo Gu, Chunxia Zhang, Xinyi Zhang, Heiying Jin
{"title":"Kiss Y flap: a novel low-tension reconstruction technique after excision of pilonidal sinus.","authors":"Jianlei Liu, Xiaochun Zhang, Xiaorui Ye, Jun Wang, Yang Yang, Jiabo Gu, Chunxia Zhang, Xinyi Zhang, Heiying Jin","doi":"10.1093/gastro/goag025","DOIUrl":"10.1093/gastro/goag025","url":null,"abstract":"","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"14 ","pages":"goag025"},"PeriodicalIF":4.2,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13005923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147505595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastroenterology ReportPub Date : 2026-03-15eCollection Date: 2026-02-01DOI: 10.1093/gastro/goag020
Ulrich Stölzel, Birgit Knoppke, Thomas Stauch, Maria I von Eichborn, Herbert L Bonkovsky, Michael Melter
{"title":"Liver graft as a 'Trojan horse': manifestation of variegate porphyria in an 11-month-old girl with biliary atresia after living-related liver transplantation.","authors":"Ulrich Stölzel, Birgit Knoppke, Thomas Stauch, Maria I von Eichborn, Herbert L Bonkovsky, Michael Melter","doi":"10.1093/gastro/goag020","DOIUrl":"https://doi.org/10.1093/gastro/goag020","url":null,"abstract":"<p><p>We report on an infant girl with biliary atresia, who, at the age of 6 months, received a living-related liver transplantation (LRLT), (segments II/III) from her 37-year-old healthy mother. Five months after LRLT, the child developed skin lesions on sunlight exposed skin areas. Based on plasma fluorescence scanning, biochemical findings and DNA testing variegate porphyria (VP) was diagnosed in the girl. In this remarkable case hepatic heme synthesis was induced in the transplanted liver through medication (metamizole), stress and infection (cholangitis), unmasking previously undiscovered partial enzyme deficiency of PPOX. LRLT with subsequent manifestation of heterozygous VP in very early childhood has not been described hitherto. Our report will increase awareness of \"rare risks\" for \"rare diseases\" in liver transplantation.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"14 ","pages":"goag020"},"PeriodicalIF":4.2,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12989146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastroenterology ReportPub Date : 2026-03-14eCollection Date: 2026-02-01DOI: 10.1093/gastro/goag019
Sara Renzo, Luca Scarallo, Nicola De Bortoli, Stefano Santi, Francesca Fierro, Paolo Lionetti
{"title":"Intraluminal dissection of the esophagus in an adolescent male: an unusual presentation of eosinophilic esophagitis successfully treated with dupilumab.","authors":"Sara Renzo, Luca Scarallo, Nicola De Bortoli, Stefano Santi, Francesca Fierro, Paolo Lionetti","doi":"10.1093/gastro/goag019","DOIUrl":"https://doi.org/10.1093/gastro/goag019","url":null,"abstract":"","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"14 ","pages":"goag019"},"PeriodicalIF":4.2,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12989144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between tomoelastography and histological grade and clinical characteristics of pancreatic neuroendocrine neoplasms.","authors":"Yu-Qing Zhong, Xi-Tai Huang, Yan-Ji Luo, Chen-Song Huang, Qiong-Cong Xu, Xiao-Yu Yin","doi":"10.1093/gastro/goag007","DOIUrl":"https://doi.org/10.1093/gastro/goag007","url":null,"abstract":"<p><strong>Background: </strong>The prognosis of a pancreatic neuroendocrine neoplasm (pNEN) is closely correlated with histological grade. While the role of tomoelastography in predicting tumor grades has been explored in various cancers, evidence regarding its association with the histological grade and clinical features of pNENs remains limited. This study aimed to investigate the association between tomoelastographic parameters and the histological grade and key clinical characteristics of pNENs.</p><p><strong>Methods: </strong>A retrospective study was conducted on 62 patients with pathologically confirmed pNENs, all of whom underwent tomoelastography prior to surgery without receiving neoadjuvant treatment. Patients were categorized into three groups: G1 (<i>n </i>= 28), G2 (<i>n </i>= 30), and G3/neuroendocrine carcinoma (NEC) (<i>n </i>= 4). The relationship between the tomoelastography parameters and clinicopathological characteristics was analysed by using the Kruskal-Wallis test, Spearman correlation, and ordinal logistic regression. Receiver-operating characteristic curves were used for evaluating the diagnostic performance of tomoelastography.</p><p><strong>Results: </strong>The shear wave speed (<i>c</i>), representing stiffness in tomoelastography, increased with tumor grade (1.63 m/s for G1 vs 2.23 m/s for G2 vs 2.53 m/s for G3&NEC, <i>P </i>< 0.001). Parameter <i>c</i> was positively correlated with the tumor size (<i>r </i>= 0.59, <i>P </i>< 0.001) and Ki67 index (<i>r </i>= 0.44, <i>P </i>< 0.001), and was notably higher in lesions with distant or regional lymph node metastases than in those without metastases. Identified as a hazardous factor for tumor grade (odds ratio = 3.92, 95% confidential interval [CI]: 1.88-8.16), <i>c</i> showed good performance in discriminating between G1 and G2 (area under the curve = 0.81, 95% CI: 0.70-0.93, <i>P </i>< 0.001).</p><p><strong>Conclusion: </strong>Tomoelastography offers a promising quantitative tool for assessing the histological grade of pNENs and identifying more aggressive tumor behavior via increased tissue stiffness.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"14 ","pages":"goag007"},"PeriodicalIF":4.2,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12987768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastroenterology ReportPub Date : 2026-03-10eCollection Date: 2026-02-01DOI: 10.1093/gastro/goag012
Olga María García-Valdeavero, Encarnación González-Flores, Raúl Ortiz, Julia Jiménez-López, Cristina Jiménez-Luna, Octavio Caba, Jose Prados, Consolación Melguizo
{"title":"Tumour Jagged1 expression as a prognostic marker of bevacizumab response and modulation of 5-fluorouracil efficacy through γ-secretase inhibition in colorectal cancer.","authors":"Olga María García-Valdeavero, Encarnación González-Flores, Raúl Ortiz, Julia Jiménez-López, Cristina Jiménez-Luna, Octavio Caba, Jose Prados, Consolación Melguizo","doi":"10.1093/gastro/goag012","DOIUrl":"https://doi.org/10.1093/gastro/goag012","url":null,"abstract":"<p><strong>Background: </strong>5-fluorouracil (5-FU)-based chemotherapy remains the backbone of metastatic colorectal cancer (CRC) treatment, although therapeutic resistance limits long-term benefit. Combination with bevacizumab improves outcomes in some patients, but biomarkers capable of predicting benefit are lacking. Notch signalling and altered expression of its ligand Jagged1 (JAG1) have been implicated in CRC progression, yet their relevance in bevacizumab-treated patients and their regulation by 5-FU remain unclear.</p><p><strong>Methods: </strong>JAG1 protein levels were quantified in tumour samples from patients with metastatic CRC (<i>n </i>= 60) by using enzyme-linked immunosorbent assay and correlated with clinical outcomes. <i>In vitro</i> experiments using HCT15 and SW480 CRC cell lines were used to assess the effects of combining 5-FU and the γ-secretase inhibitor <i>N</i>-[<i>N</i>-(3,5-difluorophenacetyl-l-alanyl)]-<i>S</i>-phenylglycine <i>t</i>-butyl ester (DAPT) on proliferation using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Notch pathway, stemness, epithelial-mesenchymal transition (EMT), and apoptosis markers were assessed by using quantitative PCR and/or Western blotting. The angiogenic capacity of the secretome was examined by using tube-formation assays.</p><p><strong>Results: </strong>Among patients receiving bevacizumab, those with low tumour JAG1 expression exhibited longer progression-free survival and time to progression than patients with high JAG1 expression. <i>In vitro</i>, DAPT plus 5-FU synergistically reduced CRC-cell viability, enhanced apoptosis and autophagy, reduced the expression of stemness and EMT-related genes, and impaired tube formation. Soluble JAG1 was detected in conditioned media, with higher levels following combination treatment in HCT15 cells.</p><p><strong>Conclusions: </strong>High tumour JAG1 expression identifies metastatic CRC patients with poorer outcomes when treated with a bevacizumab-containing regimen, supporting its potential as a prognostic biomarker. Mechanistically, Notch inhibition enhances the antitumour effects of 5-FU, suggesting that its combination with γ-secretase inhibitors may improve therapeutic efficacy in CRC.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"14 ","pages":"goag012"},"PeriodicalIF":4.2,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12975003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147437746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}