Objective To profile telomere-related genes (TRGs) to develop a robust prognostic tool for stomach adenocarcinoma (STAD) and explore their associations with immune regulation and treatment response. Methods A total of 2083 TRGs were analyzed in The Cancer Genome Atlas (TCGA)-STAD cohort (412 tumor and 36 normal samples) and external validation was performed using the GSE84437 dataset. A prognostic model was constructed through differential expression analysis, univariate Cox regression, and least absolute shrinkage and selection operator Cox regression. Model performance was evaluated using Kaplan–Meier survival analysis, multivariable Cox regression, time-dependent receiver operating characteristic curves, and nomogram construction. Associations with immune cell infiltration, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE), and drug sensitivity were assessed. The expression patterns of the signature genes were experimentally validated using quantitative reverse transcription polymerase chain reaction and Western blot analysis in human gastric cancer cell lines and an N-methyl-N′-nitro-N-nitrosoguanidine induced rat gastric adenocarcinoma model. Results An eight-TRG signature (ANXA5, ELOVL2, INCENP, NFE2L3, NOS3, RASGEF1C, REPIN1, and SOAT1) effectively predicted overall survival in the TCGA and GSE84437 cohorts, independent of clinicopathological factors (1-, 3-, and 5-year area under curves: 0.682, 0.695, and 0.697, respectively). The expression of seven genes were upregulated in tumor tissues, whereas that of RASGEF1C was downregulated. The derived risk score correlated with immune infiltration, TMB, and TIDE scores, and predicted drug sensitivities differed between the risk groups. Reverse transcription quantitative polymerase chain reaction analysis further validated the expression patterns of these genes in cell lines. In vitro and in vivo assays corroborated the bioinformatics findings, confirming the dysregulation of key signature genes in tumor cells and tissues at the mRNA and protein levels. Conclusions The eight-TRG signature provides reliable prognostic stratification for STAD and links telomere biology to the immune context and therapy response.

Introduction Precancerous lesions of gastric cancer (PLGC) represent a critical stage for intervention using traditional Chinese medicine (TCM) to prevent the development of gastric cancer (GC). As a widely used Chinese patent medicine for treating chronic gastritis in clinical practice, the molecular mechanisms of Moluodan Concentrated Pill (MLD) in PLGC remain unclear. Methods The chemical constituents of MLD were characterized using ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS), and the potential targets of its 18 herbal components were identified using the TCMSP and HERB databases. PLGC-related targets were retrieved from the DisGeNET and GeneCards databases, and the overlapping targets were identified by taking the intersection and subjected to functional enrichment analysis. A pharmacological network linking active components to shared targets was constructed, along with a protein-protein interaction (PPI) network, both visualized using Cytoscape 3.7.2. The top five hub genes identified from the PPI network, along with their corresponding active components were selected for molecular docking. Subsequently, a PLGC rat model was established using a four-factor modeling approach and treated with MLD. The findings from network pharmacology were validated through Western blotting, ELISA, HE staining, AB-PAS staining, HID-AB staining, and immunofluorescence assays. Results A total of 65 major compounds in MLD were identified. Network analysis indicated that MLD might exert its anti-PLGC effects by regulating key targets such as PI3K, AKT1, STAT3, EGFR, and SRC, thereby modulating the PI3K/AKT and EGFR signaling pathways. Moreover, its active components exhibited strong binding affinity for EGFR pathway proteins. Animal experiments demonstrated that MLD significantly alleviated pathological damage in gastric tissue, restored the ultrastructure of gastric mucosa, reduced the levels of PGC and TNF-α in peripheral blood, and downregulated the expression of PCNA, β-catenin, and EGFR in gastric mucosa. Collectively, MLD inhibited the progression of PLGC to GC by regulating the EGFR signaling axis. Conclusions MLD may exert significant therapeutic effects in PLGC by synergistically regulating multiple components and targets to modulate key signaling pathways such as PI3K/AKT and EGFR, and by inhibiting inflammation and abnormal proliferation.

Inflammatory bowel disease (IBD) is characterized by intestinal barrier dysfunction and excessive inflammation, in which STAT3 signaling plays a critical role. Berberine is clinically effective against colitis; its application is limited by low bioavailability and toxicity. Berberrubine, a major metabolite of berberine, exhibits improved pharmacological properties; however, its therapeutic potential in IBD remains unclear. The efficacy and mechanisms of berberine and berberrubine were evaluated in DSS-induced colitis mice, LPS-stimulated cells and intestinal organoids. STAT3 knockout cell lines were generated using CRISPR-Cas9 to assess the role of STAT3 in mediating the pharmacological activities of both compounds. We found that berberrubine significantly alleviated colitis, reduced pro-inflammatory cytokines (IL-6 and TNF-α), and restored intestinal barrier integrity by upregulating ZO-1 and claudin-1 in vivo and in organoids, demonstrating superior efficacy and safety to berberine. Mechanistically, both compounds inhibited STAT3 activation and nuclear translocation. STAT3 deficiency attenuated their anti-inflammatory, anti-tumor, and barrier-protective effects. Notably, berberrubine exhibited selective cytotoxicity to cancer cells over normal epithelial cells, suggesting a favorable therapeutic window. Collectively, berberrubine ameliorates intestinal barrier dysfunction and inflammation through inhibition of the STAT3 signaling pathway. Its superior efficacy and favorable safety profile compared to berberine support its potential as a novel therapeutic agent for IBD.

Gastric mucosal inflammation is a critical precondition of various gastric diseases, and development of safe and effective anti-inflammatory agents for prompt resolution of acute inflammation at early stage is vital to preventive medicine. B vitamins are essential water-soluble nutrients with reported anti-inflammatory properties, yet their potent regulatory effects in gastric mucosal inflammation are not systemically assessed. In this study, we adopted a lipopolysaccharide (LPS)-induced inflammatory mouse gastric organoid model to screen for anti-inflammatory B vitamin family members. With the anti-inflammatory effect of vitamin B12 (VB12) being validated in this gastric organoid model, which is consistent with the roles in other biological settings, further screening of the rest B vitamin members identified vitamin B6 (VB6) as the most potent anti-inflammatory agent as it preventatively ameliorated LPS-induced organoid collapse and preserved gastric epithelial polarity in the inflammatory organoids. Functional assays confirmed that VB6 significantly downregulated the expressions of key pro-inflammatory Tnf, Cxcl1, and Il1b genes, and inhibited TNF-α and IL-1β protein secretions. Further mechanistic exploration revealed that VB6 antagonized LPS-induced inflammatory responses by targeting the transcription of positive regulatory genes in core LPS-mediated inflammatory signaling pathways. These findings provide important experimental evidence for the development of nutrition-based intervention strategies for gastric inflammatory diseases in human.

BACKGROUND Gastric intestinal metaplasia (GIM) is a precancerous condition associated with gastric cancer (GC). However, biomarkers that predict progression from GIM to GC remain unclear. AIM To investigate the potential of FOLH1 as a novel tissue-based biomarker for identifying patients with GIM at high risk of progression to GC. METHODS This single-center retrospective cohort study was conducted at Wangjing Hospital and included 68 patients diagnosed with GIM. GIM samples were obtained sequentially from the antrum using endoscopic biopsies. Patients were assigned to the progressive group (P) if they developed high-grade intraepithelial neoplasia, intramucosal carcinoma, or adenocarcinoma during the 5-year follow-up; patients whose GIM remained stable were assigned to the non-progression group (N). A subset of 8 patients (4 from group P and 4 from group N) was used to identify potential biomarkers using differentially expressed genes and weighted gene correlation network analysis based on digital spatial profiling. The remaining 60 patients were used to validate candidate biomarkers using histologic evaluation, immunohistochemical staining, and immunofluorescent staining. RESULTS In the 8-patient discovery cohort, FOLH1 expression was significantly decreased in the epithelium of patients in group P compared with those in group N. In the 60-patient validation cohort, FOLH1 was a reliable biomarker for predicting malignant transformation from GIM to GC, with a sensitivity of 0.967 and a specificity of 1.000. Using Youden’s index, the optimal diagnostic cutoff value for FOLH1 was 0.302, corresponding to an integral optical density of 31.46. CONCLUSION FOLH1 may serve as a tissue-based biomarker for predicting progression from GIM to GC.

Gastric cancer (GC) is an epithelial malignant tumor with high morbidity and mortality. In recent years, more and more studies have strengthened our understanding of how GC develops, including the origin of GC cells, precancerous lesions, gene mutations, transcriptional changes, protein translation and the tumor microenvironment. With the concept of accurate tumor therapy gradually applied to clinical practice, these data provide more reference and basis for early prevention, early screening, early detection and accurate treatment of GC.

Although the eradication of Helicobacter pylori is critical for preventing gastric cancer, current therapies often overlook the restoration of the gastric microenvironment, leading to a prevalence of delayed tissue healing and dysbiosis. Consequently, many patients remain in a persistent pathological state despite successful H. pylori clearance, presenting a major bottleneck in clinical treatment. This review summarizes recent advancements in gastric-targeted drug delivery systems, illustrating the evolution from a singular antibacterial approach to an integrated sequential strategy encompassing clearance, repair, and homeostasis reconstruction. We examine smart gastro-retentive and nanodelivery systems designed to overcome physiological barriers, highlighting formulations that extend gastric residence time and maintain local drug concentrations above the Minimum Inhibitory Concentration for prolonged periods. Furthermore, we discuss spatiotemporally controllable biomaterials, such as Janus hydrogels and ROS-responsive carriers. These systems demonstrate distinct pH-dependent release kinetics and high stability in simulated gastric fluids, effectively preserving bioactive payloads to modulate the immune microenvironment. By facilitating the transition from pro-inflammatory to anti-inflammatory phenotypes, these biomaterials support epithelial regeneration. The review concludes with an analysis of postbiotics and the proposed holistic strategy, offering a promising therapeutic framework for mitigating the inflammation-to-cancer transition and promoting gastric health remodeling.

Gastric cancer arises within a complex and dynamic microenvironment shaped by gastric acid secretion, microbial communities, and chronic inflammation. While Helicobacter pylori (H. pylori ) remains the primary etiological factor, recent studies have highlighted the contribution of non-H. pylori microbiota and their interactions with host factors in the progression of gastric carcinogenesis. This review explores the bidirectional interplay among hypochlorhydria, microbial dysbiosis, and mucosal immune responses, emphasizing how this triad drives the transition from chronic gastritis to metaplasia and malignancy. We detail the ecological and functional properties of key gastric microbial taxa, examine the regulatory roles of acid and parietal cells, and discuss inflammation-mediated epithelial remodeling. In addition, we summarize advances in multi-omics technologies - including 16S rRNA sequencing, metagenomics, spatial transcriptomics, and single-cell RNA-seq-that are uncovering new dimensions of host-microbe interactions in the gastric niche. Collectively, these findings expand the classical Correa cascade into a more integrative ecosystem-based model of gastric cancer pathogenesis. While most studies remain preclinical or observational, the emerging insights provide a foundation for future investigations into risk stratification and gastric ecosystem-modulating strategies with potential relevance for prevention, early detection, and adjunctive intervention.

BACKGROUND Precancerous lesions of gastric cancer (PLGC) represent a critical pathological stage in the development of intestinal gastric cancer. Early detection and diagnosis are key to reducing the incidence of gastric cancer. Substantial advancements have been made in PLGC research in recent years, making it necessary to provide updated reviews using bibliometric methods. We hypothesize that this review will identify emerging trends, key research areas, and gaps in PLGC research, providing insights that could guide future studies and enhance prevention strategies. AIM To comprehensively review the current state of research on PLGC, examining development trends and research hotspots. METHODS We conducted a bibliometric analysis of PLGC-related studies published between 2004 and 2023 using the Web of Science Core Collection database. We employed Software, including VOSviewer, CiteSpace, R software, and SCImago Graphica, to map scientific networks and visualize knowledge trends in terms of publication volume, countries/regions, institutions, journals, authors, and keywords. RESULTS A total of 4097 articles were included, and overall publication volume showed an increasing trend. Over the past two decades, China published the most articles, followed by the United States, Japan, South Korea, and Italy. Among the top 10 contributors, the United States ranked highest in institutions, authors, and citations and demonstrated the strongest international collaboration. Research keywords in this field were clustered into three main categories: Risk factors, pathogenesis, and diagnosis and treatment. Pathogenesis and molecular biomarkers remain key areas of focus. Future research should explore the mechanisms of gut microbiota, immune microenvironment, metabolic reprogramming, and epigenetics. Advanced technologies, including single-cell sequencing, spatially resolved analysis, multi-omics approaches, artificial intelligence, and machine learning, will likely accelerate in-depth investigations of PLGC. CONCLUSION PLGC research has rapidly developed in recent years, gaining considerable attention. This bibliometric analysis reveals research state and emerging trends over the past 20 years, providing insights for future studies.

Tumor-associated macrophages (TAMs), which differentiate from tissue-resident macrophages, are recognized for their ability to influence cancer progression and metastasis. However, the specific role of Kupffer cells (KCs), the intrinsic macrophages of the liver, in the progression of hepatocellular carcinoma (HCC) remains unclear. In this study, we describe a novel mechanism by which exosomes derived from HCC cells induce KCs to transition into TAMs, thereby facilitating the metastasis of HCC in an IL6-JAK1-ACAP4 axis-dependent manner. Mechanistically, the exosome-mediated domestication of KCs by hepatoma cells constitutes one of the primary sources of IL6 production in the HCC microenvironment. IL6 then activates JAK1 to phosphorylate its downstream effector ACAP4 at Tyr843, a novel phosphorylation site identified in this context, which in turn promotes ARF6-GTPase activity and hepatoma cell migration. Furthermore, we found that the levels of IL6, as well as the phosphorylation of JAK1 and ACAP4 at Tyr843, were significantly greater in tumor tissues from HCC patients than in adjacent tissues. These findings suggest that the IL6-JAK1-ACAP4 axis may be a promising therapeutic target for HCC. Importantly, we screened bufalin, an active ingredient derived from Venenum Bufonis, and discovered that it inhibits JAK1 and disrupts the IL6-induced phosphorylation of ACAP4. This inhibition not only impairs hepatoma cell migration but also prevents the metastasis of HCC. These findings demonstrate the interplay between hepatoma cells and KCs through the IL6-JAK1-ACAP4 axis, thereby promoting HCC metastasis, and reveal the therapeutic potential of bufalin for the treatment of HCC through JAK1 inhibition.

Modernizing traditional Chinese medicine (TCM) requires preserving its foundational principles while integrating contemporary innovations and clarifying therapeutic methods. Organoids and organoids-on-chip technologies offer advanced models of human organs, and serve as an excellent platform for investigating TCM theories and complex herbal formulas. To systematically summarize recent progress in using organoids and organoids-on-chip in TCM research, and critically assess their technical advantages and future potential, relevant articles and information were sourced from scientific databases such as PubMed, SpringerLink, Web of Science, ScienceDirect, and VIP. The application of organoids and organoids-on-chip technologies in TCM research encompasses theory interpretation, efficacy evaluation, mechanism elucidation, toxicity assessment, active ingredient screening, and formula optimization. These applications offer significant advantages, such as unveiling holistic effects, deciphering mechanistic bases through dynamic visualization approaches, and demonstrating personalized therapeutic benefits. Enhancing physiological relevance, automation, and intelligent applications are future development directions. Organoids and organoids-on-chip represent transformative tools for the modernization of TCM. Future advancements in vascularization, neural network development, and the integration of artificial intelligence are anticipated to address existing limitations, thereby enhancing physiological relevance and clinical translation. These advancements are expected to promote global acceptance and innovation in TCM.

ETHNOPHARMACOLOGICAL RELEVANCE:Yinmeikuijie decoction (YMKJD), a traditional Chinese herbal formulation, has demonstrated clinical efficacy in alleviating ulcerative colitis (UC). However, its underlying therapeutic mechanisms remain poorly understood. AIM OF THE STUDY:We aimed to assess the therapeutic efficacy of YMKJD against UC and to unravel its underlying mechanisms through both in vivo and in vitro investigations. MATERIALS AND METHODS:Dextran sulfate sodium (DSS)-induced murine UC model mice, TNF-α-treated Caco-2 cells, LPS-stimulated RAW264.7 macrophages, and colon organoids were utilized to investigate YMKJD's therapeutic effects. Macrophage polarization (M1/M2 subsets) was assessed via flow cytometry and immunofluorescence. Immunofluorescence staining and Western blot were performed to evaluate the intestinal epithelial barrier (IEB). Untargeted metabolomics, transcriptomic sequencing, and network pharmacology were integrated to elucidate key pathways. Candidate targets were further verified using qRT‒PCR and Western blot. RESULTS:YMKJD administration markedly improved clinical symptoms and mitigated colonic tissue damage in UC mice. YMKJD attenuated IEB disruption in vivo and in vitro. Mechanistically, combined bioinformatics and experimental analyses revealed that YMKJD downregulated the expression of the key enzymes (COX-2, 5-LOX, PTGES) in the arachidonic acid (AA) metabolism, thereby suppressing proinflammatory mediators (Leukotriene B4, Prostaglandin E2, ROS) and inhibiting PI3K/AKT signaling in inflamed epithelial cells. Interestingly, YMKJD also blocked COX-2-driven M1 polarization in macrophages, diminishing ROS levels in cocultured colon organoids. Rescue studies confirmed that AA metabolism activation counteracted YMKJD's protective effects in both animal and cellular UC models. CONCLUSIONS:Our findings demonstrate YMKJD's therapeutic potential and its mechanism in UC, suggesting its utility as a novel treatment strategy.

Introduction: Inflammatory breast cancer (IBC) is a highly aggressive subtype of breast cancer associated with a poor prognosis. A better understanding of IBC’s pathological and molecular basis is crucial for developing precision medicine strategies. Objective: This study aimed to profile IBC at both the single-cell and spatial levels to examine immune cell populations, signaling pathways, and identify potential therapeutic targets for treating IBC. Methods: Single-cell RNA sequencing (scRNA-seq) was employed to identify immune-related differences between IBC and non-IBC samples. qRT-PCR and fluorescence staining were utilized to validate the findings from scRNA-seq, while spatial analysis using the NanoString GeoMx Digital Spatial Profiler was conducted to evaluate immune cell infiltration. Tumor-immune cell co-culture assays were conducted to assess the cytotoxic role of CXCL13. In vivo studies were performed to assess the effect of CXCL13 on the efficacy of immunotherapy. Furthermore, a screening of natural products was performed to identify potential immunomodulatory agents for the treatment of IBC. Results: scRNA-seq revealed a significant reduction in CXCL13 expression in T cells within the IBC tumor microenvironment, a finding that correlated with poorer patient outcomes. Additionally, immune-related gene sets were notably downregulated, and cell–cell interactions were diminished, indicating a state of immune suppression within IBC. Spatial analysis further demonstrated a reduced presence of CD45-positive immune cells within IBC tumor tissues, highlighting the compromised immune infiltration characteristic of this aggressive cancer subtype. Most importantly, overexpression of CXCL13 in tumor cells, under co-culture with immune cells, significantly promoted tumor cell death. CXCL13 can also enhance the efficacy of anti-PD-1 therapy in vivo. Furthermore, screening of natural products identified sanguinarine and α-mangostin as potential immunomodulatory compounds, offering promising therapeutic avenues for modulating the immune response in IBC and improving treatment outcomes. Conclusion: Our findings reveal inherent heterogeneity within the “cold” tumor microenvironment of IBC. These factors collectively contribute to the immune suppression characteristic of IBC. Additionally, natural product screening identified sanguinarine and α-mangostin as promising immunomodulatory agents, offering potential therapeutic strategies to improve treatment outcomes.

Background Bladder cancer (BLCA) is a challenging malignancy with a poor prognosis, particularly in muscle-invasive cases. Despite recent advancements in immunotherapy, response rates remain suboptimal. This study investigates the role of METTL3, an m6A RNA methylation “writer,” in regulating the immune microenvironment of BLCA.Methods Through bioinformatics analysis, we identified METTL3 as being associated with the formation of an immunosuppressive microenvironment in BLCA and poor response to immunotherapy. Subsequently, we silenced METTL3 expression in BLCA cells using short hairpin RNA (shRNA) or inhibited its function with STM2457. The effectiveness of these interventions in remodeling the BLCA tumor microenvironment (TME) was confirmed through animal experiments and flow cytometry. Mechanistically, RNA sequencing and methylated RNA immunoprecipitation (MeRIP) sequencing revealed the molecular pathways by which METTL3 regulates the TME. This was further validated using in vitro cell co-culture, immunoprecipitation, ELISA, and RNA degradation assays. The synergistic effect of METTL3 with anti-Programmed Cell Death Protein 1 (PD-1) treatment in BLCA was confirmed in both orthotopic and ectopic BLCA animal models.Results METTL3 was found to increase CXCL5 levels and suppress CCL5 expression in an m6A-dependent manner, leading to increased recruitment of myeloid-derived suppressor cells (MDSCs) and reduced infiltration of CD8+T cells. Silencing METTL3 or inhibiting its function restored immune cell balance and significantly enhanced the efficacy of anti-PD-1 therapy. Clinically, METTL3 overexpression correlated with poor complete response rate to immune checkpoint inhibitors (ICIs) therapy, associated with an immunosuppressive microenvironment characterized by elevated MDSC levels and reduced CD8+T cell infiltration.Conclusions These findings highlight METTL3 as a key regulator of the immune microenvironment in BLCA and a promising therapeutic target to improve immunotherapy outcomes. Targeting METTL3 could potentially enhance the efficacy of ICIs in patients with BLCA.

Colonization of Helicobacter pylori (H. pylori) in stomach often causes gastritis, an inflammation of the stomach lining that is closely associated with serious conditions like ulcers and gastric cancer. Of the toxicity mechanisms, microbial lipopolysaccharide (LPS) binding to TLR4 receptor on the glandular cells activates the NF-κB pathway, inducing pro-inflammatory cytokine release and immune cell infiltration, which results in the tissue damage. However, whether LPS has any direct damaging effect on gastric epithelial cells has been in debate. By using mouse gastric organoids that were grown from the isolated glands and maintained the cellular compositions, we demonstrate various effects of variable LPS concentrations on the glandular epithelial cells, including mild promotion of cell proliferation at the low concentration and induced loss of cell polarity and altered gene expressions at the high concentration. These findings provide insights into how LPS directly affects the stomach lining.

Cell migration requires the generation of branched actin networks and recruitment of vesicular membrane that power the protrusion of the plasma membrane in lamellipodia. However, the molecular mechanisms underlying dynamic recruitment of vesicular membrane during cell migration remain elusive. Here, we report a critical mechanism underlying epidermal growth factor (EGF)-elicited Akt signaling-steered cell migration. Using functional proteomics screen, we identified a novel ADP-ribosylation factor 6 (ARF6)-ACAP4 signaling regulator, Acapin, which inhibits the GTPase-activating protein (GAP) activity of ACAP4 to activate ARF6 GTPase in vitro. In cells, EGF stimulation elicits Akt signaling, which recruits Acapin to the lamellipodium membrane via phosphorylation of Acapin at its Ser247 residue and enhances the binding of Acapin to ACAP4 to elevate the ARF6-GTP level. Therefore, Acapin is required for efficiently stimulating cell migration by EGF-Akt signaling. Together, our results demonstrate the role of Acapin in relaying the Akt signaling cascade during cell migration processes.

Metabolic reprogramming has recently been recognized as related to immune disorders in ulcerative colitis (UC), but the specific metabolic pathways and genes involved remain unclear. Here, Mendelian randomization confirmed that mannose and mannonate exhibited a negative causal relationship with UC, and that the immune cell phenotype HLA DR on CD33dim HLA DR+ CD11b- mediated the effect of mannonate on UC. Bulk RNA sequencing data revealed that mannose metabolism abnormity is critical for driving the innate and acquired immune response. A well-performing diagnostic model related to mannose metabolism was constructed using SVM analysis, achieving an AUC-ROC value of 0.987 in the training set and an AUC-ROC value of 0.899 in the validation set. Single-cell analysis revealed that epithelial cells in which the mannose metabolism pathway was inactivated demonstrated increased intercell communication with myeloid cells, T cells, and B cells. In vitro experiments confirmed that KHK and AKR1B10 were suppressed under inflammatory stimulation, which may hinder mannose-related metabolism. This study elucidates the protective role of mannose metabolism in UC and provides a novel gene signature for diagnosis and treatment.

Gastric intestinal metaplasia (GIM) represents a precancerous stage characterized by morphological and pathophysiological changes in the gastric mucosa, where gastric epithelial cells transform into a phenotype resembling that of intestinal cells. Previous studies have demonstrated that the intragastric administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces both gastric carcinoma and intestinal metaplasia in mice. Here, we show that MNNG induces GIM in three-dimensional (3D) mouse organoids. Our histological analyses reveal that MNNG-induced gastric organoids undergo classical morphological alterations, exhibiting a distinct up-regulation of CDX2 and MUC2, along with a down-regulation of ATP4B and MUC6. Importantly, metaplastic cells observed in MNNG-treated organoids originate from MIST1+ cells, indicating their gastric chief cell lineage. Functional analyses show that activation of the RAS signaling pathway drives MNNG-induced metaplasia in 3D organoids, mirroring the characteristics observed in human GIM. Consequently, modeling intestinal metaplasia using 3D organoids offers valuable insights into the molecular mechanisms and spatiotemporal dynamics of the gastric epithelial lineage during the development of intestinal metaplasia within the gastric mucosa. We conclude that the MNNG-induced metaplasia model utilizing 3D organoids provides a robust platform for developing preventive and therapeutic strategies to mitigate the risk of gastric cancer before precancerous lesions occur.

[This corrects the article DOI: 10.1016/j.cellin.2024.100147.].

BACKGROUND Hepatic organoid-based modelling, through the elucidation of a range of in vivo biological processes and the recreation of the intricate liver microenvironment, is yielding groundbreaking insights into the pathophysiology and personalized medicine approaches for liver diseases. AIM This study was designed to analyse the global scientific output of hepatic organoid research and assess current achievements and future trends through bibliometric analysis. METHODS Articles were retrieved from the Web of Science Core Collection, and CiteSpace 6.3.R1 was employed to analyse the literature, including outputs, journals, and countries, among others. RESULTS Between 2010 and 2024, a total of 991 articles pertaining to hepatic organoid research were published. The journal Hepatology published the greatest number of papers, and journals with an impact factor greater than 10 constituted 60% of the top 10 journals. The United States and Utrecht University were identified as the most prolific country and institution, respectively. Clevers H emerged as the most prolific author, whereas Huch M had the highest number of cocitations, suggesting that both are ideal candidates for academic collaboration. Research on hepatic organoids has exhibited a progressive shift in focus, evolving from initial investigations into model building, differentiation research in stem cells, bile ducts, and progenitor cells, to a broader spectrum encompassing lipid metabolism, single-cell RNA sequencing, and therapeutic applications. The phrases exhibiting citation bursts from 2022 to 2024 include “drug resistance”, “disease model”, and “patient-derived tumor organoids”. CONCLUSION Research on hepatic organoids has increased over the past decade and is expected to continue to grow. Key research areas include applications for liver diseases and drug development. Future trends likely to gain focus include patient-derived tumour organoids, disease modelling, and personalized medicine.