bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0192 Activities of Sorghum bicolor diet on microbial gut-brain axis during experimental Crohn’s Colitis in adult male Wistar rats
Authors: Salami PhD A T , Akpamu U , Anyakudo G C , Oluwakorede T S , Olujimi A O , Olaleye B S 
Published: January 2025

Abstract

Background
Crohn’s colitis (CC) is a form of inflammatory bowel disease with increasing resistance to synthetic medications hence the search for easily-accessible medicinal plants with anti-inflammatory activities. During CC, there are reports of dysbiosis, neuro-inflammation accompanied with defective brain structure, irregular neural signaling, and associated depressive-like behavior. Sorghum bicolor leaf (SBLD) and seed (SBSD) are accessible medicinal plant with anti-inflammatory bioactive compounds. However, there is limited information regarding its activities on microbial-gut-brain axis during CC which this study evaluates.

Methods
Ethical approval was obtained from the University of Ibadan (UI-ACUREC/071-1222/31) and S.bicolor plant was identified by the institutional herbarium (UIH-23294). Eighty male Wistar rats (100-150g, n=10) were divided thus: Groups 1-normal rats, 2-colitis untreated (CCU), 3-CC+Azathioprine, 4-CC+Resveratrol, 5-CC+10% SBLD, 6-CC+20% SBLD, 7-CC+10% SBSD, 8-CC+20% SBLD. Groups 2-8 were induced with CC (1ml/kg of 1.4% NaOH single intra-rectal) by day 14 of treatment which continued for 7 days. Daily body weights, neuro-behavioural studies, and stool score were monitored. Animals were euthanized, and colon was excised for ulcer score. The excised colon and brain were submitted for biochemical estimation and histological processing and evaluation by days 3 and 7 post CC induction. Fecal samples were processed for gut microflora using 16S rDNA gene sequencing. Results were subjected to one-way ANOVA, values expressed as MEAN±SEM and statistically significant at p≤0.05.

Results
Body weight, colon weight/length ratio, stool and ulcer scores in SBLD and SBSD-treated groups significantly reduced compared with CCU, and CC+Resveratrol on days 3 and 7. Colon healing zone, and neuro-behaviour traits (rearing, grooming, and line crossing time) in SBLD and SBSD-treated groups significantly increased compared with CCU. Colon and brain malondialdehyde, carbonyl, nitric oxide, significantly reduced but increased in hydrogen peroxide, mucin, sulfhydryl, glutathione-reductase, and calcium ATPase pump activities in the SBLD and SBSD-treated groups compared with CCU on both days. Reactive cortico-hippocampal cells in SBLD and SBSD-treated groups significantly reduced compared with CCU, CC+Azathioprine and CC+Resveratrol. Lactobacillus species in the SBLD and SBSD-treated groups significantly increased compared with CCU on both days.

Conclusion
Sorghum bicolor leaf and seed diet facilitated healing of Crohn’s colitis and attenuated adverse neurobehavioural traits through reduced oxidative stress, and increased gut Lactobaccillus sp. with gut-brain signaling.
P0198 Comparative Transcriptomic Analysis of Tonsil-derived and Adipose-derived Mesenchymal Stem Cells: Proliferation, Migration, and Anti-inflammatory Potential in Murine Colitis Model
Authors: Song E M , Joo Y H , Byeon J , Choe A R , Park Y , Tae C H , Kim S E , Jung H K , Shim K N , Jung S A 
Published: January 2025

Abstract

Background
Tonsil-derived mesenchymal stem cells (TMSCs) have emerged as a promising alternative to traditional MSCs due to their rapid proliferation and accessibility. This study explores the unique transcriptomic and cellular properties of TMSCs compared with adipose-derived MSCs (AMSCs).

Methods
TMSCs and AMSCs were cultured under identical conditions in low-glucose DMEM with 10% FBS. Proliferation was evaluated via CCK-8 assays, and migration potential was assessed using scratch assays. Transcriptomic differences were analyzed using RNA sequencing, with key findings validated by qPCR.

Results
TMSCs displayed distinct morphological features compared to AMSCs, with TMSCs showing a spindle shape, while AMSCs appeared more irregular and rounded shape. In terms of proliferation, TMSCs demonstrated a significantly higher proliferation rate by day 7 (245.3% of control vs. 134.4% of control, p &lt; 0.001). However, there was no significant difference in migration capacity between TMSCs and AMSCs over a 24-hour period (50.8 ± 8.2 vs. 53.8 ± 9.8, p = 0.537). RNA sequencing analysis revealed notable differences in gene expression, with TMSCs showing enrichment in pathways related to extracellular matrix, cell adhesion, and immune response, particularly with upregulation of the MAPK signaling pathway compared with AMSCs. For anti-inflammatory cytokines, IL-33, FOXF1, and HGF were upregulated in TMSCs relative to AMSCs. In relation to proliferation and migration, CCL2, CXCL12, and STC1 levels were also higher in TMSCs. Additionally, TMSCs exhibited increased expression of RAB27B, suggesting a greater potential for exosome release. In a DSS-induced acute colitis model, both TMSCs and AMSCs alleviated colitis symptoms with significant improvements in colon length (p &lt; 0.05). Real-time PCR analysis of mouse colonic tissue also demonstrated a reduction in pro-inflammatory cytokines, such as IL-1β, with TMSCs showing a more pronounced reduction.

Conclusion
This study demonstrates that TMSCs possess unique characteristics, including a higher proliferation rate and distinct gene expression profiles compared to AMSCs. While both MSC types exhibited similar anti-inflammatory effects in murine colitis model, the enhanced anti-inflammatory potential and increased exosome release capacity of TMSCs, combined with their easy availability, highlight their promise for clinical application.
P0205 Fecal host transcriptomics accurately assesses endoscopic inflammatory activity in patients with inflammatory bowel diseases
Authors: Weintraub Y , Segal A , Matar M , Nevo-Shor A , Kantor I , Shamir R , Bahar Halpern K , Itzkovitz S , Yehuda-Cohen A , Kahan-Hanum M , Harnik Y , Shouval D 
Published: January 2025

Abstract

Background
The intestinal mucosa regenerates every few days, and cells are continuously shed into the gut lumen. These cells, primarily epithelial and immune cells, have recently been shown to remain viable after shedding and hold critical information for assessing bowel pathology. Analysis of endoscopic washes of luminal material during colonoscopies suggests that the human transcriptome in fecal material accurately reflects degree of histologic inflammation in patients with inflammatory bowel diseases (IBD). We aimed to define whether transcriptomic analysis of stool samples can reflect degree of intestinal inflammation in patients with IBD.

Methods
Bulk RNA sequencing was performed on stool samples to obtain fecal human transcriptomes from 82 IBD patients, as well as from healthy controls. Each sample received an inflammation score derived from a group of pro-inflammatory transcripts. Inflammatory score was compared to fecal calprotectin as well as endoscopic evaluation.

Results
The quality of human RNA isolated from fecal content was high, with a median of 2,218 human genes detected per sample. The correlation between fecal calprotectin protein levels and mRNA expression was high (r=0.75). An inflammatory score was generated based on a group of differentially expressed genes. The inflammatory score provided high sensitivity and specificity (both 90%) in predicting endoscopic inflammatory activity when compared to colonoscopic findings.

Conclusion
Fecal shed cell transcriptomics provided a novel non-invasive tool to measure inflammatory activity at the endoscopic level in patients with IBD. Ongoing studies will address whether this technology can assist in defining degree and location of inflammation, as well as predict response to different therapies.
P0212 Non-canonical STING signaling in intestinal epithelial cells guides DNA damage-driven stem cell function and protects from intestinal carcinogenesis
Authors: Xiang H , Woitaske-Proske C , Bernardes J P , Martini G R , Wottawa F , Bornhaeuser J , Kakavand N , Guang Y , Wu Q , Kugler J , Welz L , Konukiewitz B , Peifer C , Schreiber S , Tschurtschenthaler M , Rosenstiel P , Aden K 
Published: January 2025

Abstract

Background
RNaseH2 plays a critical role in removing mis-bounded RNA from the DNA double strand helix1. Absence of RNaseH2 results in spontaneous double-stranded DNA breaks and cytosolic release of dsDNA2. We have previously shown that epithelial deficiency of RNaseH2b (H2bΔIEC) leads to a p53-dependent stem cell suppression and additional deficiency of p53 results in spontaneous intestinal carcinogenesis3. Due to the central role of cGAS/STING in sensing dsDNA, we aim to investigate the role of epithelial STING in a mouse model of chronic epithelial DNA damage and tumor prevention in this study.

Methods
DNA damage was assessed using comet assay in ModeK cell line with cGAS and STING knock out. Protein kinase activity were assessed by Pamgene Kinase Assay. Intestinal organoids were generated from H2bΔIEC and H2bΔIEC/Tmem173-/-mice. Colony forming assay and EdU staining were performed in all genotypes to assess the impact of STING on epithelial stem cell function and proliferation were assessed by CellTiter Glo assay.
RNA sequencing was performed in intestinal organoids. Spontaneous carcinogenesis was assessed in 1-year aged mice.

Results
Loss of RNaseH2b results in activation of cGAS/STING pathway and subsequent upregulation of IFN-I signature. Deficiency of cGAS/STING lead to impaired IFN-I independent DNA damage repair which were accessed by WB and comet assay. During the DNA damage response, STING but not cGAS mediates the P53 pathway and the P21-CDK axis. Organoid EdU stanning displayed restored proliferation in H2bΔIEC/Tmem173-/- compared to H2bΔIEC. RNA sequencing from H2bΔIEC/Tmem173-/-organoid further confirmed decreased G2/M DNA damage checkpoint and P53 signature compared to H2bΔIEC. In vivo, we show that H2bΔIEC/Tmem173-/- mice have downregulated DNA damage repair and developed spontaneous small bowel adenocarcinoma after 53 weeks. Tumor derived from H2bΔIEC/Tmem173-/- mice show sensitivity to CDK inhibitor consistent with in vitro validation.

Conclusion
We provide evidence that non-canonical role of epithelial STING mediates DNA damage response and guides P21-CDK1 axis in preventing tumor genesis. Our research provided evidence understand the role of STING in DNA damage response and intestine carcinogenesis.

References
1.Reijns, Martin A.M., et al., Enzymatic Removal of Ribonucleotides from DNA Is Essential for Mammalian Genome Integrity and Development. Cell, 2012. 149(5): p. 1008-1022.
2.Bartsch, K., et al., Absence of RNase H2 triggers generation of immunogenic micronuclei removed by autophagy. Hum Mol Genet, 2017. 26(20): p. 3960-3972.
3.Aden, K., et al., Epithelial RNase H2 Maintains Genome Integrity and Prevents Intestinal Tumorigenesis in Mice. Gastroenterology, 2019. 156(1): p. 145-159 e19.
P0214 Notch Pathway-Mediated epithelial-mesenchymal transition and Fibrosis in Complicated Crohn’s Disease
Authors: Patel J , Cejudo-Garcés A , Jarén A , Macias-Ceja D C , Manresa M , López A , Cosin-Roger J , Calatayud S , Barrachina M D , Ortiz-Masiá D 
Published: January 2025

Abstract

Background
The dysregulation of epithelial-mesenchymal transition (EMT) is linked to numerous pathologies, including fibrotic diseases. The Notch pathway may selectively mediate fibrogenic processes, such as EMT. Previous studies by our group have demonstrated elevated expression of NOTCH3, NOTCH4 receptors, and the DLL4 ligand in the intestines of patients with complicated Crohn’s disease (CD)1. This study aims to explore the potential of the Notch pathway as a therapeutic target in intestinal fibrosis associated with CD.

Methods
We analyzed ileal samples from Crohn’s disease patients with complicated lesions to assess the localization of NOTCH3/4 receptors using immunohistochemistry (IHQ) and performed RT-qPCR and Western blot (WB) analysis. In vitro studies were conducted using DLL4-coated plates (1 µg/ml), with or without the γ-Secretase Inhibitor DAPT (10 μL/ml), to evaluate protein and mRNA expression of HES1 and EMT markers (VIMENTIN, SNAIL, and E-CADHERIN) in two primary epithelial cell lines: small intestine (HIEC6) and colon (CoEpi) cells over 48 hours. Data, presented as fold induction (mean ± SEM) relative to water-treated cells or control tissues, were analyzed using parametric or non-parametric ANOVA (Kruskal-Wallis) based on normality testing (*P &lt; 0.05).

Results
RT-qPCR analysis revealed significantly increased mRNA levels of the Notch receptors NOTCH3 and NOTCH4. WB analysis showed elevated levels of NOTCH3 (235±87*), but not NOTCH4 (87±13), protein in affected versus control tissues (100±8 and 100±7, respectively). In terms of cellular localization, NOTCH3 was detected in endothelial and smooth muscle cells, lamina propria cells, and with lower intensity in the epithelium. NOTCH4 was primarily found in cells of the lamina propria. In vitro assays indicated that DLL4 significantly altered mRNA and protein expression of HES1 and certain EMT markers (VIMENTIN and SNAIL) in both epithelial cell lines. Co-treatment with DAPT significantly reversed some EMT markers induced by DLL4 (VIMENTIN and SNAIL) (Figure 1).

Conclusion
NOTCH3 may play a role in the fibrogenic processes of CD, with elevated expression observed. The activation of EMT markers by DLL4 suggests that Notch signaling has a critical function in driving fibrosis and tissue remodeling in CD.

References
M Rodriguez-Antequera, J Cosin-Roger, D Macias-Ceja, P Salvador, L Gisbert-Ferrándiz, S Coll, J Manyé, R Alós, F Navarro-Vicente, S Calatayud, M D Barrachina, D Ortiz-Masia, P041 Differences in NOTCH signalling between stricturing and penetrating behaviour in Crohn’s disease, Journal of Crohn’s and Colitis, Volume 13, Issue Supplement_1, March 2019, Page S107, https://doi.org/10.1093/ecco-jcc/jjy222.165
P0224 Learning Curve in Intestinal Ultrasound: Advancing from Basic Skills to Advanced Competencies – Insights from the IUS IG-IBD (Italian Group for the Study of Inflammatory Bowel Disease) Master Program
Authors: Bezzio C , Pitoni D , Ribaldone D G , Vernero M , Castiglione F , Rispo A , Saibeni S , Maconi G , Terracciano F , Bossa F , Allocca M , Furfaro F , Calabrese E , Zorzi F , Fraquelli M , Caprioli F , Rizzello F , Mazzotta E , Orlando A , Grova M , Massironi S , Viganò C , Armuzzi A 
Published: January 2025

Abstract

Background
Intestinal ultrasound (IUS) is increasingly used in assessing Crohn’s disease (CD) and ulcerative colitis (UC) due to its accessibility, low cost and absence of radiation. However, its operator dependency necessitates targeted training programs. This study aimed to evaluate the learning curve of gastroenterology trainees in IUS, determining the number of exams required to achieve diagnostic agreement with expert tutors.

Methods
This study was conducted at eight Italian referral centers for intestinal ultrasound as part of the IUS Master promoted by IG-IBD. Eight gastroenterology trainees with significant experience in abdominal ultrasound but limited exposure to IUS each performed 99 consecutive examinations. The trainees received an eight-hour course on IUS and one week of hands-on training with the expert sonographer. The exams were divided into three periods of 33. After each examination, an expert sonographer reassessed the findings and Cohen's Kappa coefficient was used to measure the agreement between the trainee and the expert operator for all the parameters considered. The parameters considered were bowel wall thickening, vascularity, Limberg score and complications (fistulas, stenosis, abscesses).

Results
A progressive improvement in concordance was observed across all parameters from period 1 to period 3 for all learners (Table 1). Overall agreement in identifying pathological findings increased from K=0.778 to K=0.911. Specifically, concordance for bowel wall thickening improved from K=0.558 in the first 33 exams to K=0.780 in later periods. Vascularity reached K=0.909 and the Limberg score achieved K=0.879. For complications, agreement on fistulas increased from K=0.765 to K=0.893, while stenosis improved from K=0.583 to K=0.872. Abscesses consistently demonstrated high concordance (K=0.855). The number of examinations required to achieve good agreement with the expert operator for detecting bowel wall thickening was at least 66, while 69 were needed for the accurate assessment of increased vascularity. However, detecting intra-abdominal complications required at least 99 examinations.

Conclusion
The time required to achieve proficiency in assessing intestinal ultrasound parameters related to the bowel wall is shorter than the time needed to detect the presence of complications. These findings highlight the importance of structured and supervised practice to achieve proficiency in both basic and advanced IUS competencies, providing a foundation for the development of standardized training programs in gastroenterology.
P0226 Postoperative recurrence after a definitive ostomy in Crohn's disease. A nationwide retrospective series from the Eneida registry
Authors: Calafat Sard M , Mañosa M , Fernández-Clotet A , Pasanau L , Matallana V , Iglesias E , Hernández-Camba A , Ucha P , Nos P , Barrio J , Gutiérrez A , Merino V , Barreiro-de Acosta M , Cudero L , Casanova M J , González-Muñoza C , Bujanda L , Varela P , Bermejo F , Torres N , Mesonero F , Calvet X , Rivas C , Pérez C , Alonso-Abreu I , Rodríguez-Lago I , Vega P , Zabana Y , Mora M , Busquets D , Rodríguez-Gutiérrez C , Torres G , Valldosera G , Ponferrada Á , Ceballos D , Martínez Pascual C , Jiménez N , Sampedro M , Irabien M , Domènech E 
Published: January 2025

Abstract

Background
Although the concept of postoperative recurrence (POR) in Crohn’s disease (CD) has been limited to patients undergoing intestinal resection with anastomosis, some small-sized retrospective series with short follow-up periods suggest that clinical POR may occur in up to 30% of patients with a definitive ostomy. This may explain the lack of recommendations for monitoring and preventive strategies in this clinical setting. Our aim was to assess the risk of POR and current monitoring strategies in this population.

Methods
Retrospective study from the ENEIDA database of GETECCU. Patients with CD and a permanent ostomy were included. Demographic, clinical characteristics, evolution, and monitoring data were analyzed.

Results
Overall, 263 patients who underwent permanent ostomy between 1979 and 2023 were included, of whom 70% had an ileostomy and 30% a colostomy with 65% having previous ileal involvement in both groups. Proctectomy had been performed in 57% of them. Medical prevention for POR was started in 38% of patients (44% thiopurines, 43% biologics, and 13% 5ASA). Regarding monitoring strategies in asymptomatic patients, 25% underwent ileoscopy, 43% had radiological examinations and 53% faecal calprotectin measurements. Moreover, 37% underwent radiological examinations and 55% ileoscopy due to the development of symptoms or elevation of biomarkers.
After a median follow-up of 142 months (IQR 75-267), 32% developed clinical POR, 16% biological POR, 37% endoscopic POR, 37% radiological POR, and 14% surgical POR. Among those with POR, 37% started medical therapy (9% 5ASA, 24% thiopurines, 65% biologics). The cumulative probability of clinical POR at 3, 5, and 10 years was 16%, 20%, and 28%, respectively. The cumulative probability of surgical POR at 3, 5, and 10 years was 5%, 8%, and 12%, respectively. In the multivariate analysis, risk factor for clinical POR was having colostomy vs. ileostomy (OR 2.05, 95% CI 1.05-3.99; P=0.035).
As for complications during follow-up, 40%, 24%, and 18% of patients developed iron-deficiency anemia, vitamin B12 deficiency, or renal insufficiency, respectively.

Conclusion
More than one third of patients with CD and a permanent ostomy develop POR in the long-term, and 10% requiring a new resection. These findings underscore the need for recommendations on monitoring strategies and preventive approaches n this clinical scenario.
P0230 Prognostic factors and predictive model development for pediatric Inflammatory Bowel Disease with IL-10RA deficiency: A retrospective cohort study
Authors: Shi X , Qian L , Wu H , Wang L , Ye Z , Dong K , Sun S , Zhai X , Qian X , Huang Y 
Published: January 2025

Abstract

Background
Patients with IL10RA-deficient inflammatory bowel disease (IBD) generally have a poor prognosis, with high mortality and a significant rate of intestinal surgeries. Hematopoietic stem cell transplantation (HSCT) is currently the main cure, but most patients still face death after transplantation. The study analyzes the prognosis of patients without HSCT, aiming to explore factors associated with both mortality and the need for intestinal surgery, as well as to establish short-term prognostic models.

Methods
The study retrospectively enrolled 138 patients admitted to our center from January 2012 to July 2024. We defined death and intestinal surgery as outcomes and used competing risks analysis, cox regression models, and random survival forest algorithm to explore prognostic factors. Additionally, optimal subset regression, and logistic regression were employed to establish a short-term prognostic model, with the goal of better assessing the severity of the patients' conditions and evaluating the likelihood of long-term survival, as well as the risks of short-term death or surgery.

Results
The median age of onset of 138 patients was 0.3 months (range: 0.2-1 months), and the median age of admission was 8.1 months (range: 3.0-15.2 months). 21.7% had pure homozygous mutations. The most frequent was c.301C&gt;T，c.537G&gt;A. 32.6% of patients died, of which 73.3% were transplant-related. 35.5% of patients had undergone intestinal surgery. In patients without HSCT, most deaths occurred within the first year, while intestinal surgeries were mainly performed by age four. Cox multivariate analysis identified thalidomide used as an independent protective factor against mortality (HR = 0.09, 95% CI: 0.02-0.46, P = 0.004). Intestinal perforation was a significant risk factor (HR = 9.39, 95% CI: 3.49-25.30, P &lt; 0.001) for the outcome of intestinal surgery. The random survival forest model highlighted thalidomide, mesalazine, intestinal perforation and gross bloody stool as key variables affecting mortality or surgery risk, with thalidomide having the greatest impact. Short-term death model (age of admission, ALB, intestinal perforation) was well distinguished (AUC: 0.945), but poorly calibrated; Short-term surgical models (CRP, PLT, perianal lesions) were moderately distinguished (AUC: 0.799), and the calibration was reasonable.

Conclusion
Long-term survival is possible for IL10RA-deficient patients without HSCT. However, due to the risk of early-life adverse outcomes, close follow-up remains essential. Thalidomide appears to have the most significant impact on prognosis and may improve disease outcomes. The short-term prognostic assessment model demonstrates good discriminatory ability for distinguishing high-risk from low-risk patients.