Introduction

Treatment response in inflammatory bowel disease (IBD) is highly variable, with an urgent need for biomarkers to guide therapeutic decisions. Circulating monocytes, key players in intestinal immunity, act as precursors to tissue macrophages and contribute to inflammation and mucosal healing. The transcriptional programs that govern monocyte fate and their association with treatment outcomes remain poorly defined. Ikaros family proteins regulate gene expression through distinct mechanisms in lymphocytes, but little is known about their role in monocyte-macrophage function in IBD. We aimed to investigate the role of Ikaros family (Ikaros, Helios, Aiolos, Eos, Pegasus) in shaping monocyte function linked to advanced therapies response.

Aims & Methods

Peripheral blood samples were collected at baseline (W0) and after 8-12 weeks of induction therapy (W8/12) from IBD patients who initiated or switched advanced therapy [biologics, oral synthetics] and from healthy controls (HC) (n=8). We included patients achieving clinical remission after induction [Super-Responders] SR (n=18) and those showing no response [Non-Responders] NR (n=16). Immune phenotype and expression of Ikaros proteins were assessed via multiparametric flow cytometry (FACS) and correlated with clinical outcomes. To assess functional roles of Ikaros proteins, monocyte-derived macrophages were generated in vitro from buffy coat (n=6). Cells were polarised using cytokine cocktails to induce pro-inflammatory (LPS+IFNγ or TNF+PGE2+Pam3CSK4; TPP), alternative (IL1β+LPS), or regulatory (IL10) phenotypes. siRNA-loaded nanoparticles were used to silence Ikaros or Helios prior to polarisation. Phenotypic changes were analysed by FACS; cytokines secretion by ELISA; genes expression by qPCR; and phagocytosis by fluorescent beads uptake.

Results

At W0, IBD patients exhibited a significant increase in circulating monocyte counts (vs HC, p<0.001). At W8/12, monocyte levels significantly decreased in the SR group, while remaining elevated in the NR group. FACS analysis revealed an increased proportion of non-classical monocytes (CD14⁻CD16⁺) in the IBD group at W0 (vs HC; p< 0.05), persisting in NR at W8/12 (vs SR; p<0.05). IBD monocytes also showed higher expression of CCR2 and CX3CR1 compared to HC. Helios expression was absent in monocytes from IBD patients at W0, while the mean expression of Helios was 47.31% in monocytes from the HC group. At W8/12, Helios expression re-emerged in 34.14% of monocytes derived from the SR patients but remained undetectable in the NR. In vitro, macrophages treated with LPS+IFNγ or TPP upregulated Ikaros, STAT1, and CXCL10 gene expression (p< 0.01), while Helios, TGM2, and MCR1 were upregulated in response to IL10 (p< 0.05). Helios expression was absent in TNF-stimulated macrophages. Ikaros silencing reduced pro-inflammatory markers, IL6 and IL1β cytokines secretion, and inhibited phagocytosis in response to LPS, whereas Helios silencing increased macrophages activation, and pro-inflammatory markers in response to IL10.

Conclusion

Monocyte subsets distribution and Helios, Ikaros expression dynamics clearly distinguished SR from NR in IBD. Sustained absence of Helios and persistence of non-classical monocytes in NR suggest a failure to transition toward a regulatory phenotype. This may further contribute to altered migratory capacity and influence their functional fate within intestinal tissue. Functional assays confirm opposing roles of Ikaros and Helios in the macrophages activation, underscoring their unique potential as biomarkers or therapeutic targets to modulate inflammation in IBD.

Introduction

Helicobacter pylori (H. pylori) induces epithelial DNA damage and genomic instability to promote gastric carcinogenesis. Ubiquitination modifications mediate the specific degradation of intracellular proteins and broadly regulate cellular life activities. However, the molecular mechanism by which H. pylori infection drives the E3 ubiquitin ligase TRIM47 to promote gastric mucosal carcinogenesis remains unclear.

Aims & Methods

This study employed gastric cancer cells, gastric organoids, human tissues, and mouse models. H. pylori infection was established in both in vitro and in vivo models. Functional and mechanistic investigations were conducted using Western blotting, qRT-PCR, co-immunoprecipitation, immunofluorescence, and immunohistochemistry to explore the role of H. pylori in promoting DNA damage in gastric epithelial cells through TRIM47-mediated ubiquitination and degradation of STAT1.

Results

Validation in human cells, gastric organoids, and gastric tissues revealed that H. pylori upregulates TRIM47 expression via its virulence factor CagA. Knockdown of TRIM47 in cells significantly suppressed H. pylori-induced DNA damage. Ubiquitination proteomic sequencing and subsequent validation demonstrated that TRIM47 degrades STAT1 via ubiquitination, with the TRIM47 RING domain serving as a critical functional site. Overexpression of TRIM47 in gastric organoids markedly attenuated H. pylori-induced STAT1 activation.

Conclusion

This study identifies the E3 ubiquitin ligase TRIM47 as a critical mediator of H. pylori-induced DNA damage in gastric epithelial cells. TRIM47 promotes gastric mucosal lesions following H. pylori infection by facilitating STAT1 ubiquitination and degradation.

Disclosure

The authors declare that they have no conflicts of interest.

Introduction

Underwater endoscopic mucosal resection (UEMR) is an alternative to conventional EMR (CEMR) offering consistent negative horizontal margins. However, UEMR does not involve submucosal injection; thus, its ability to achieve a sufficient resection depth comparable to that of CEMR remains uncertain. This randomized controlled trial (RCT) aimed to compare UEMR and CEMR in terms of resection depth.

Aims & Methods

This multicenter, parallel two-arm, open-label, noninferiority RCT was conducted across four Japanese institutions enrolling patients with colorectal tumors measuring 10–20 mm. Participants were randomly assigned in a 1:1 ratio to either to UEMR or CEMR group, using a computerized random-number generator. The primary outcome was the resection depth, which is the distance from the lower edge of the muscularis mucosa to the deep margin of the resected specimen, analyzed based on per-protocol (PP) principles (noninferiority margin of 400 µm).

Results

This study screened 217 patients from September 21, 2022, to December 2, 2024, and randomly assigned them to the UEMR (n =109) or CEMR (n =108) group. The PP analysis revealed that the mean resection depths of the UEMR and CEMR groups were 1688.9 ± 1510.0 µm and 1432.3 ± 1294.2 µm, respectively (mean difference: 256.6 µm, 95% confidence interval: -119.9 µm to 633.1 µm; P = 0.18), indicating the noninferiority of UEMR compared with CEMR in terms of resection depth. Subgroup analyses revealed that the resection depth of lesions by UEMR, especially at the cecum/ascending colon (1822.4 ± 1469.7 µm vs. 1096.5 ± 1007.6 µm; P = 0.01), and those with superficial morphology (1238.7 ± 862.2 µm vs. 731.6 ± 376.1 µm; P < 0.01), was significantly deeper than that achieved by CEMR. Moreover, even for nonexperts, UEMR tended to provide adequate resection depth compared with CEMR, approaching the proficiency level exhibited by experts (1786.6 ± 1471.6 µm vs. 1192.4 ± 1074.7 µm; P = 0.07). There were no significant differences in adverse events between the two groups, including one case of intraoperative perforation (0.9%) in the CEMR group and one case of delayed bleeding (0.9%) in the UEMR group. No EMR-related deaths were reported.

Conclusion

UEMR maintains the equivalent resection depth as CEMR and could become the gold standard endoscopic resection technique for intermediate-size colorectal tumors. UEMR is strongly recommended, especially for lesions at the cecum, ascending colon, and superficial lesions, because it could resect significantly deeper than CEMR. Furthermore, UEMR is recommended for nonexperts as a resection method that provides sufficient resection depth (Clinical trial registration number: UMIN000047432).

Introduction

Functional gastrointestinal disorders (FGIDs), such as irritable bowel syndrome (IBS) and functional dyspepsia, are prevalent conditions within the field of Neurogastroenterology. These disorders have a profound impact on patients’ quality of life and demand a comprehensive biopsychosocial approach to care. Despite evidence in favor of integrated care, treatment remains largely pharmacological. To address this gap, our hospital established a dedicated Functional Neurogastroenterology Unit by incorporating a nurse trained in health coaching and Neuro-Linguistic Programming (NLP) supported by a custom GPT-based artificial intelligence (AI) tool aimed at enhancing patient communication and clinical decision-making.

Results & Findings

A descriptive observational study was conducted on nurse-led consultations between September 2024 and April 2025. The intervention integrated coaching sessions, Neuro-Linguistic Programming (NLP), and the use of a customized GPT-based system to support communication and care planning. Data collected included demographic characteristics, presenting symptoms, and referral patterns. Additionally, each patient was invited to write a personal narrative reflecting on their experience throughout the intervention.

Summary & Discussion

Forty-eight patients were attended during the study period (mean age: 38.6 years; 68.7% female). The most common diagnoses were functional dyspepsia, irritable bowel syndrome, and nonspecific digestive disorders. Frequently reported symptoms included bloating, epigastric pain, early satiety and burning. 20.8% of patients were referred to psychology services and 2.1% to psychiatry. Patient narratives revealed improvements in emotional self-regulation, greater sense of empowerment, and high levels of satisfaction. AI reduced administrative burden, improving focus on direct care, interdisciplinary communication, and adherence to treatment.

Conclusion

Coaching, NLP and AI are effective tools to address FGIDs from nursing, promoting personalized care and improving the patient's emotional well-being.

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