The intestinal mucus barrier has emerged as a promising therapeutic target for inflammatory bowel disease. Understanding its regulatory mechanisms is critical for elucidating ulcerative colitis (UC) pathogenesis, improving diagnostics, guiding treatments, and preventing relapse. Chloride Channel Accessory 1 (Clca1), a constituent of the mucus layer, remains understudied in colitis. Here, we investigated Clca1's role in mucosal immunity and intestinal homeostasis using experimental colitis models. Clca1-deficient (Clca1-/-) mice displayed compromised mucus layer integrity, reduced neutrophil infiltration, and gut microbiota dysbiosis. Notably, Clca1-/- mice exhibited exacerbated colitis severity following dextran sulfate sodium (DSS) challenge, accompanied by a diminished goblet cell populations. Fecal microbiota transplantation (FMT) studies revealed that gut microbiota critically modulates divergent phenotypic outcomes between genotypes. Our findings establish Clca1 as a multifunctional regulator of mucus barrier integrity through mechanisms involving goblet cell maintenance, neutrophil-mediated immunity, and host-microbiota crosstalk. These results advance the understanding of UC pathogenesis and identify Clca1-associated pathways as potential targets for barrier restoration therapies.

The development of effective and safe dietary supplements is essential for both the prevention and management of ulcerative colitis (UC), as its pathogenesis is intricate and difficult to completely resolve. Crataegus pinnatifida, a medicinal food with a long history of use, has broad medicinal value. Recent research has revealed promising insights into the role of polysaccharide derived from Crataegus pinnatifida on modulating short-chain fatty acids (SCFAs) to alleviate UC inflammation. However, the mechanisms by which CPP regulates the intestinal microbiota and key metabolites during the antagonistic phase of UC have yet to be elucidated.

This research elucidated the protective role of CPP in relation to UC, highlighted the mechanisms through which CPP operates, particularly regarding gut microbiota and metabolism, and offered a theoretical foundation for the potential use of CPP as a dietary supplement aimed at preventing UC.

The impact of CPP on acute UC induced by 3 % DSS in mice was examined through the evaluation of the disease activity index, measurement of colon length, and observation of body weight changes. Enzyme-linked immunosorbent assay (ELISA) was used to measure inflammatory factor levels in both serum and colon, as well as to assess oxidative stress mediators. The intestinal histological damage, mucus layer damage and the level of tight junction protein were analyzed by histopathological staining and western blot (WB). The impact of gut microbiota on CPP in colitis was evaluated using 16S rRNA sequencing, microbiota depletion experiments, and fecal microbiota transplantation (FMT) studies. The key metabolic pathways and key metabolites affected by CPP in the treatment of UC were analyzed through untargeted metabolomics sequencing, ELISA, and WB assays.

Prophylactic dietary supplementation with Crataegus pinnatifida polysaccharide (CPP) notably reduced the fundamental clinical manifestations of UC induced by DSS, including DAI score, reduced colon length, and weight loss, as well as inflammation and oxidative stress. CPP promoted the expression of Claudin-1, ZO-1 and Occludin and promoted mucin secretion, which contributed to the mitigation of intestinal barrier damage caused by DSS. 16S sequencing results and metabolomics results revealed that CPP intervention upregulated the relative abundance of Lactobacillus, thereby reshaping the intestinal microbiota and activate the arginine biosynthesis pathway. The results of fecal microbiota transplantation and antibiotic clearance experiments indicated that the alleviating effect of CPP on UC was dependent on the intestinal microbiota and this alleviating effect was transferred through fecal microbiota transplantation. Mechanistically, CPP indirectly promoted the expression of the rate-limiting enzyme argininosuccinate synthase 1 (ASS1) in the intestinal Arginine biosynthesis pathway by reshaping the intestinal microbiota, thereby increasing intestinal Arginine level and alleviating the inflammatory response and oxidative stress induced by DSS and intestinal barrier damage.

Our research findings demonstrate that CPP is a plant-derived polysaccharide that alleviates UC by modulating the gut microbiota and enhancing arginine biosynthesis.

The treatment of ulcerative colitis (UC) remains a huge challenge worldwide. Dictamnine is a natural product derived from Dictamnus dasycarpus Turcz. root bark and possesses multi-pharmacological properties, including anti-inflammation effects. However, its protective effect on UC and its underlying mechanisms are unknown.

Here we explored the protective effect and underlying mechanism of dictamnine against dextran sulfate sodium (DSS)-induced colitis in mice.

The experimental colitis was established by adding 3% DSS on drinking water of mice and the effects of dictamnine (10, 20, 40 mg/kg, p.o, once a day by 10 days) in colon tissues was analyzed. NCM460 cell was induced by RSL3 to detect the effect of dictamnine on ferroptosis and the underlying mechanism. Pathological damage was determined by H&E. Indicators related to intestinal permeability were detected by FITC and immunofluorescence. Cytokines levels (TNF-α、IL-1β and IL-6), antioxidant enzymes activities (MDA and GSH), the level of Fe2+ Cytokines levels and Gpx4 activity were detected by ELISA. Finally, the activation of nuclear factor erythroid 2-like 2 (Nrf2) was detected to explore the mechanism.

The results indicated that dictamnine significantly attenuated DSS-induced colon pathological damage, intestinal barrier, cytokines levels, and increased the antioxidant enzymes activities. Moreover, dictamnine attenuated ferroptosis in DSS-induced colon injury and upregulated Gpx4 expression in DSS-induced mice. Mechanistic experiments revealed that dictamnine activated Nrf2 in mice.

Taken together, this study evaluates that dictamnine alleviates DSS-induced colitis mice by inhibiting ferroptosis of enterocytes and its protective effects are associated with activating the Nrf2-Gpx4 signaling pathway.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by increased stool frequency, rectal bleeding, and urgency. To streamline the quantitative assessment of histopathology using the Nancy Index in UC patients, we developed a novel artificial intelligence (AI) tool based on deep learning and tested it in a proof-of-concept trial. In this study, we report the performance of a modified version of the AI tool.

Nine sites from 6 countries were included. Patients were aged ≥18 years and had UC. Slides were prepared with hematoxylin and eosin staining. A total of 791 images were divided into 2 groups: 630 for training the tool and 161 for testing vs expert histopathologist assessment. The refined AI histology tool utilized a 4-neural network structure to characterize images into a series of cell and tissue type combinations and locations, and then 1 classifier module assigned a Nancy Index score.

In comparison with the proof-of-concept tool, each feature demonstrated an improvement in accuracy. Confusion matrix analysis demonstrated an 80% correlation between predicted and true labels for Nancy scores of 0 or 4; a 96% correlation for a true score of 0 being predicted as 0 or 1; and a 100% correlation for a true score of 2 being predicted as 2 or 3. The Nancy metric (which evaluated Nancy Index prediction) was 74.9% compared with 72.3% for the proof-of-concept model.

We have developed a modified AI histology tool in UC that correlates highly with histopathologists' assessments and suggests promising potential for its clinical application.

Atractylodes lancea (Thunb.) DC. is used in China as a folk medicine for gastrointestinal disorder treatment, and its effect on treating gastrointestinal disorders is enhanced when it is fried in bran. Atractylodes lancea rhizome polysaccharide (ALP) are a group of active substances in Atractylodes lancea rhizome,ALP has good anti-inflammatory, oxidative, immunological, and intestinal flora-regulating activities, suggesting that it is a potential drug option for treating ulcerative colitis (UC). However, the effects and mechanisms of raw Atractylodes lancea rhizome polysaccharide (SALP) as well as bran-fried Atractylodes lancea rhizome polysaccharide (FALP) on dextran sodium sulfate (DSS)-induced UC in mice are unclear.

This study aimed to investigate the comparative therapeutic effects of SALP and FALP in mice with UC and assess their potential mechanisms of action.

BALB/c mice were regularly administered 3.5 % DSS to develop and establish an acute UC model, following which SALP-L, SALP-H, FALP-L, FALP-H and sulfasalazine (SASP) were administered for 10 days continuously. The body weight, disease activity index (DAI), organ index, colon length, histopathological damage, proinflammatory cytokine expression level, tight junction protein expression, transcriptome, metabolomics, and 16S rDNA of the mouse model were examined to compare the efficacy and mechanisms of action of SALP and FALP in UC treatment.

Both SALP and FALP significantly alleviated clinical signs (increased body weight, decreased DAI scores, reduced colonic pathological damage, and others), improved intestinal barrier (promoted Occludin and ZO-1 expression), and reduced intestinal inflammation (inhibited IL-1β and TNF-α [proinflammatory cytokines] expression) in DSS-induced acute UC mice. Metabolomics revealed that both SALP and FALP reversed arachidonic acid, lactic acid, ethanolamine, 9,12-octadecadienoic acid, phosphoric acid, and 1-monopalmitin levels in colonic tissues. In addition, they attenuated intestinal flora disorders in DSS-treated mice by increasing the relative abundance of the beneficial bacteria Lachnospiraceae_NK4A136_group and Alistipes while decreasing that of the harmful bacteria Alloprevotella and Prevotellaceae_UCG_001. Of note, the improvement effect of FALP was better than that of SALP in these results.

Both SALP and FALP reduced colitis symptoms by repairing the intestinal barrier, modulating intestinal flora, and improving the metabolism of compounds in colonic tissues. Of note, The therapeutic effects of FALP were all stronger than those of SALP.

Current treatment of ulcerative colitis (UC) remains challenging, with the mainstay of therapy being 5-aminosalicylic acid-based drugs, which have limited and inconsistent results. Atractylodes macrocephala (AM) is a traditional Chinese medicine commonly used in the clinical treatment of various inflammatory diseases. Herein, we demonstrate that AM-derived extracellular vesicle-like particles (AMEVLP) can effectively modulate the gut microbiota, thereby significantly improving the treatment efficiency of UC. This is achieved by enhancing the alpha diversity of the gut microbiota and re-establishing beneficial types, which in turn alter tryptophan metabolism, leading to an increase in indole derivatives within the gut. This process also protects the gut barrier and exerts anti-inflammatory effects. The mechanism behind these anti-inflammatory effects is closely associated with the Th17 cell differentiation signaling pathway. It is believed that the AMEVLP enable them to efficiently remodel gut microbiota, providing an avenue for the treatment of various inflammatory diseases. Significantly, preliminary clinical trials have shown that AMEVLP can substantially slow the progression of the disease in UC patients.

Inflammatory bowel disease (IBD), particularly ulcerative colitis (UC), is a chronic inflammatory disorder characterized by an unclear etiology, often linked to gut microbiota dysbiosis and immune dysregulation. Existing UC therapies are constrained by suboptimal efficacy and adverse effects, underscoring the necessity for novel therapeutic strategies. Diosmin (DIO), a naturally occurring flavonoid, has demonstrated anti-inflammatory and antioxidant potential, yet its precise mechanisms and therapeutic role in colitis remain poorly understood.

This study aimed to investigate the therapeutic efficacy and mechanistic underpinnings of DIO in dextran sulfate sodium (DSS)-induced colitis, with a focus on its effects on intestinal epithelial cell PANoptosis, gut microbiota composition, fecal metabolites, and an in vitro inflammatory model using human colonic epithelial cells.

A controlled experimental design was employed, utilizing a DSS-induced murine colitis model and an LPS-induced inflammatory model in human colonic epithelial cells (NCM460). Mice were allocated into four groups: normal control, DSS-induced colitis, low-dose DIO (DIO-L, 100 mg/kg), and high-dose DIO (DIO-H, 200 mg/kg). In vitro experiments involved treating NCM460 cells with varying DIO concentrations post-LPS stimulation to assess its impact on inflammation and epithelial barrier integrity.

Mice were administered DIO orally at 100 mg/kg or 200 mg/kg daily. Therapeutic outcomes were evaluated through body weight monitoring, Disease Activity Index (DAI) scoring, and histopathological examination. Gut microbiota composition was analyzed via 16S rRNA sequencing, while untargeted metabolomics was employed to profile fecal metabolites. Data integration was performed using O2PLS and WGCNA to identify microbiota-metabolite correlations. In vitro, immunofluorescence staining and Western blotting were utilized to evaluate the expression of tight junction proteins (ZO-1, E-cadherin, and Occludin).

DIO administration significantly ameliorated colitis symptoms in mice, as evidenced by attenuated weight loss, reduced DAI scores, and preserved colon length. Histopathological analysis confirmed diminished inflammation and tissue damage in DIO-treated groups. Mechanistically, DIO suppressed the expression of PANoptosis-associated genes and proteins, including ZBP1 and Caspase-1, while maintaining epithelial barrier integrity in vitro. Furthermore, DIO modulated gut microbiota composition, promoting beneficial taxa such as Ruminococcus and reducing pathogenic Proteobacteria. Metabolomic profiling revealed alterations in key metabolic pathways, including flavonoid and steroid hormone biosynthesis, which correlated with microbiota changes.

DIO effectively mitigates DSS-induced colitis by inhibiting intestinal epithelial cell PANoptosis, preserving barrier function, and modulating gut microbiota and metabolite profiles. These findings highlight DIO's potential as a therapeutic agent for IBD and warrant further exploration of its clinical applications.

The inflammatory response is the core mechanism of the pathogenesis and symptoms of ulcerative colitis (UC), and inhibiting inflammation is a promising therapeutic approach to improving UC. Curcumin is considered a potential treatment for UC due to its significant anti-inflammatory and antioxidant effects. However, its bioavailability in the post-oral administration is limited. Therefore, the stability, sustained release, and colon targeting of curcumin in the treatment of UC have become a challenge. Herein, curcumin was efficiently filled in the porous structure of University of Oslo 66 (UiO-66). Amino-functionalized UiO-66 (MOF) was bound to hyaluronic acid (HA) via chemical crosslinking and electrostatic interactions. Polydopamine (PDA) layer was then applied to form Cur@MOF@HA-PDA NPs for colon targeting for UC treatment. Cur@MOF@HA-PDA NPs not only enhanced the stability of curcumin but also possessed acid resistance and reactive oxygen species (ROS) responsive properties, enabling it to be effectively delivered to the UC lesion site for curcumin release after oral administration, thereby enhancing the therapeutic effect. In vitro studies revealed that Cur@MOF@HA-PDA NPs possessed the ability to eliminate intracellular ROS, inhibit inflammatory (M1) polarization, and promote anti-inflammatory (M2) polarization. Additionally, in vivo experiments demonstrated that Cur@MOF@HA-PDA NPs could effectively alleviate the intestinal inflammatory symptoms of UC mice, promoting intestinal tissue repair. Furthermore, it was also confirmed that Cur@MOF@HA-PDA NPs achieved the treatment of UC by inhibiting inflammatory responses, modulating intestinal immune functions, and promoting the polarization of M2 macrophages. In short, Cur@MOF@HA-PDA NPs, as colon-targeted drug delivery nanosystems, offer a promising therapeutic strategy for the treatment of UC.

Ulcerative colitis is an idiopathic and chronic inflammatory bowel disease, characterized by inflammation of the mucosa of the colon and rectum. Clinical manifestations commonly include abdominal pain, diarrhea (with or without hematochezia), and weight loss. The pathogenesis of ulcerative colitis is multifactorial, involving a combination of genetic predispositions and lifestyle factors. High consumption of processed food, sedentary habits, alcohol intake, and stress are among the lifestyle factors implicated in disease onset and progression. Current treatment strategies focus on managing symptoms and inducing remission, however, the chronic nature of the disease, along with the adverse effects of conventional therapies, often compromises patient's quality of life. Therefore, exploring alternative therapies that can prolong remission and reduce symptom burden is important. Experimental evidence suggests that probiotics may extend remission duration in ulcerative colitis. Moreover, probiotics exhibit efficacy in amelioration clinical symptoms by reducing inflammation markers, preserving, and restoring intestinal epithelial. This review explores the advantages of the administration of probiotics in the treatment of ulcerative colitis, elucidating their mechanism of action.

Ulcerative colitis (UC) is an inflammatory bowel disease with an unknown cause. Previous studies have shown that Group 3 innate lymphoid cells (ILC3s) are crucial for maintaining intestinal mucosal immune homeostasis by producing key cytokines such as IL-22 and IL-17 A. While the RNA-binding protein Musashi-2 (MSI2) is recognized as essential for promoting intestinal epithelial regeneration post-injury, its impact on immune regulation remains unclear. Therefore, we aim to investigate the protective mechanisms associated with ILC3s-specific MSI2 deletion in a mouse model of ulcerative colitis.

Dextran sulfate sodium (DSS) was used to induce a mouse colitis model. Colitis severity was evaluated through weight loss, diarrhea, fecal traits, colon length, and pathological scoring. Transcriptome sequencing was utilized to identify differentially expressed genes in colon tissues. Flow cytometry was employed to measure the quantity and functionality of ILC3s. Western blot was conducted to analyze protein expression, while real-time polymerase chain reaction and enzyme-linked immunosorbent assay were employed to quantify inflammatory factors. Additionally, immunofluorescence, AB-PAS staining, and immunohistochemistry were employed to evaluate the integrity of the intestinal barrier.

Following DSS treatment, colon damage was milder in Msi2∆Rorc mice than in Msi2fl/fl mice. Transcriptomic analysis revealed the down-regulation of cytokines and pro-inflammatory factors in the colon tissue of Msi2∆Rorc mice. Flow cytometry showed that specific deletion of MSI2 reduced the infiltration of ILC3s in the intestinal lamina propria of Msi2∆Rorc mice and decreased IL-17 A production. The reduction of IL-17 A-mediated immune responses lessened inflammatory damage to the intestinal barrier, thereby reducing colitis severity.

Specific deletion of MSI2 alleviates DSS-induced colitis in mice by reducing ILC3s infiltration and IL-17 A secretion in the lamina propria of the colon. This decrease in inflammatory mediators and cell infiltration dampens the inflammatory response in the intestinal mucosa, helping to maintain the integrity of the intestinal barrier in mice with colitis. These findings enhance our understanding of UC pathogenesis and offer novel avenues for clinical diagnosis and treatment.

For severe forms of ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), biological therapies, including tumor necrosis factor inhibitors (anti-TNF), are often used. However, these drugs have a high variability in treatment response. Multiple factors, such as genetic variants, can affect this variability. The goal of the study was to verify if selected candidate variants could affect response to anti-TNF in UC treatment. This association study included 76 participants suffering from UC and past or current users of anti-TNF. Clinical data for phenotyping was collected through a single visit with the participant and a medical chart review. Blood or saliva samples were collected to extract DNA and to genotype eight selected candidate variants in genes TNF, TNFAIP3, TNFRSF1 A and TNFRSF1B. For anti-TNF users, 30% of individuals were non-responders, 70% suffered from AE and none of the studied variants was associated with the response's phenotype. However, for infliximab users only (n = 44), the TNFRSF1B-rs1061622 variant was associated with nonresponse to infliximab for the first time in a cohort of UC patients (p-value = 0.028). Next steps are to replicate this association in independent cohorts and to perform functional studies to gain more evidence on the variant.

JiuLiWan (JLW), as a classic traditional Chinese medicine formula, has been clinically used against ulcerative colitis (UC). However, the exact mechanism of its therapeutic effect remains unclear. This study aims to explore and validate the main components and pharmacological mechanism of JLW in the treatment of UC through network pharmacology, molecular docking, and cell experiments. Network pharmacology analyses indicated a total of 107 main components and 286 core targets of JLW against UC. Pathway enrichment analysis demonstrated the involvement of PI3K-AKT, MAPK, Ras, Rap1, TNF, T cell receptor, HIF-1, C-type lectin receptor, VEGF, and Th17 cell differentiation signal pathways in the efficacy of the formula. The molecular docking results indicated that the prominent components (ailanthone (AIL), butylidenephthalide, honokiol, dehydrocostuslactone, ganoderic acid A, atractylenolide I, neokurarinol, glycyrrhetinic acid, palmatine, tangeretin, and bruceine A) could bind to core targets AKT1, P53, STAT3, c-JUN, and ERK1. Subsequently, AIL was used as a representative compound to conduct cell experiments to verify its role and mechanism in anti-inflammation and immunomodulation. Interestingly, AIL could switch Jurkat T cells into a quiescence state without activating the inflammatory and immune status. However, AIL could significantly decrease the levels of interleukin-2 (IL-2) and interferon-gamma (IFN-γ), as well as the expression of surface activation markers CD69 and CD25, in PMA/ionomycin-activated Jurkat T cells by suppressing the RAF/ERK/STAT3 signaling pathway and increasing the phosphorylation of p53. This study combines network pharmacology prediction with experimental verification in vitro to demonstrate the mechanism of JLW in treating UC and provides an effective, safe, and inexpensive strategy for UC treatment.

Liupao tea is known for its anti-inflammatory antioxidant and regulation of gut microecological balance properties. This study aims to investigate the therapeutic effects of Liupao tea aqueous extract (LPTAE) on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in rats. The rats were randomly divided into five groups: the Normal group, the DSS group, the LPTL group, the LPTM group, and the LPTH group. Throughout the experiment, the rats' activity levels, stool consistency, and body weights were observed and recorded daily. After the experiment, colon length was measured, and colon tissues were collected for pathological analysis. Additionally, the colon contents were analyzed for gut microbiota composition and short-chain fatty acid (SCFA) level, while serum samples were collected to determine inflammatory and oxidative factors. The results indicated that treatment with low, medium, and high doses of LPTAE significantly inhibited weight loss, alleviated rectal bleeding, and reduced colon shortening compared to the DSS group. It also decreased the disease activity index and histopathological activity index scores in the rats. Furthermore, LPTAE reduced the levels of inflammatory cytokines such as IL-1β, IL-6, TNF-α, and malondialdehyde, while simultaneously increasing the levels of superoxide dismutase and SCFAs, including acetic acid, propionic acid, and butyric acid. 16S rDNA gene sequencing of the gut microbiota revealed that all doses of LPTAE reversed the decrease in both α and β diversities caused by UC, increased the relative abundance of beneficial bacteria such as Lactobacillus, Muribaculaceae, Alloprevotella, and Blautia, and decreased the levels of harmful bacteria such as Prevotella, Romboutsia, and Bacteroides. In summary, within the tested doses (100, 150, 250 mg/kg), LPTAE alleviated DSS-induced colitis by modulating the gut microbiota and correcting the metabolic imbalance of SCFAs.

Gegen Qinlian Decoction (GQD), a classic decoction documented in the Treatise on Febrile Diseases, is clinically used to treat ulcerative colitis (UC). However, the active components and underlying pharmacological mechanisms of GQD in UC remain inadequately explored. Herein, we identify the active components and elucidate the underlying pharmacological mechanisms of GQD in the treatment of UC. A mouse model of UC was induced using dextran sulfate sodium (DSS) and treated with low, medium, and high doses of GQD. The therapeutic effects were assessed by monitoring body weight, disease activity index (DAI), colon length, spleen index, pathological changes, and cytokine levels. Plasma biomarkers were analyzed using Ultra-Performance Liquid Chromatography Quadrupole-Orbitrap mass spectrometer (UPLC-Q-Orbitrap MS)-based metabolomics. Changes in gut microbiota were also examined to identify key microbes involved in the intestinal pathological shifts. Additionally, network pharmacology analysis was conducted to predict the potential pathways of GQD in UC, which were subsequently validated by western blotting and ELISA assays. GQD significantly improved UC symptoms.A total of 98 chemical constituents in GQD were identified. Of these, 25 differential metabolites were found between normal and UC mice, with GQD modulating 22 of these metabolites. Metabolic pathways related to tryptophan, arginine, and proline were normalized. Network pharmacology predicted the apoptosis pathway as a potential target for GQD in UC intervention. Further experiments confirmed that GQD reduced pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and downregulated the Bax/Bcl-2 apoptosis pathway. Moreover, gut microbiota analysis showed that GQD enhanced the diversity and abundance of beneficial bacteria. GQD alleviates UC by modulating tryptophan, arginine, and proline metabolism, maintaining gut microbiota balance, and reducing apoptosis in intestinal cells.

Sini Decoction (SND), a time-honored formulation in traditional Chinese medicine, consists of three key ingredients: aconite, licorice, and ginger rhizome. It has been used for more than a thousand years to relieve symptoms associated with acute gastroenteritis, dyspepsia, and abdominal discomfort, but its therapeutic efficacy in ulcerative colitis (UC) and the mechanisms involved have not been validated. In this study, a comprehensive approach integrating network pharmacology, molecular docking, molecular dynamics simulation and experimentation was used to assess the efficacy of SND in the treatment of UC and to explore its molecular mechanisms.

The bioactive compounds associated with ulcerative colitis (UC) were identified using the TCMSP database, with potential targets predicted via the Swiss Target Prediction database. Protein-protein interaction networks were constructed using the STRING database and Cytoscape and the most important genes were identified. Subsequently, molecular docking was combined with molecular dynamics simulations using molecular docking to assess the binding affinity of the main active ingredient of SND to AKT1. To evaluate the therapeutic effects of SND, we utilized a dextran sodium sulfate-induced UC mouse model. Additionally, fecal samples were collected for analysis of the intestinal microbiota to explore the influence of SND on gut flora composition.

Fifteen bioactive components from SND were identified, and their activities were validated. The results indicated that AKT serine/threonine kinase 1 is a core target of SND for the treatment of UC. The anti-inflammatory, intestinal barrier-protective, and microbiota-regulating effects of SND were confirmed in animal models, alongside evidence of its inhibitory effect on AKT1.

The active ingredients of SND were screened, with a focus on AKT1 inhibition, to reduce inflammation in UC, protect the intestinal barrier, and regulate the intestinal microbiota, demonstrating significant therapeutic potential.

This study investigates the effect and underlying mechanism of targeting SLC7A11 in mitigating dextran sulfate sodium (DSS)-induced intestinal inflammation and injury in colitis.

We utilized wild-type and SLC7A11-/+ mice to assess the inflammatory damage in DSS-induced colitis in vivo. In vitro, colon tissues from patients with ulcerative colitis were analyzed to compare SLC7A11 expression between inflamed and non-inflamed regions. Further mechanistic insights were obtained using Caco-2 cells and bone marrow-derived dendritic cells (BMDCs).

In human colon tissues, SLC7A11 expression was significantly elevated in inflamed regions compared to non-inflamed areas, particularly in dendritic cells. In vivo inhibition of SLC7A11 markedly alleviated DSS-induced colitis symptoms. In vitro, suppressing SLC7A11 restored the integrity of the Caco-2 monolayer intestinal epithelial model. Both knockout and inhibition of SLC7A11 enhanced ERK1/2 phosphorylation and increased efferocytosis in BMDCs.

Targeting SLC7A11 augments dendritic cell efferocytosis and preserves intestinal epithelial barrier function, potentially offering a therapeutic avenue for alleviating ulcerative colitis.

Ulcerative colitis (UC), a chronic relapsing-remitting inflammatory bowel disease. Recent studies have shown that lactylation modifications may be involved in metabolic-immune interactions in intestinal inflammation through epigenetic regulation, but their specific mechanisms in UC still require in-depth validation.

We conducted comparative analyses of transcriptomic profiles, immune landscapes, and functional pathways between UC and normal cohorts. Lactylation-related differentially expressed genes were subjected to enrichment analysis to delineate their mechanistic roles in UC. Through machine learning algorithms, the diagnostic model was established. Further elucidating the mechanisms and regulatory network of the model gene in UC were GSVA, immunological correlation analysis, transcription factor prediction, immunofluorescence, and single-cell analysis. Lastly, the CMap database and molecular docking technology were used to investigate possible treatment drugs for UC.

Twenty-two lactylation-related differentially expressed genes were identified, predominantly enriched in actin cytoskeleton organization and JAK-STAT signaling. By utilizing machine learning methods, 3 model genes (S100A11, IFI16, and HSDL2) were identified. ROC curves from the train and test cohorts illustrate the superior diagnostic value of our model. Further comprehensive bioinformatics analyses revealed that these three core genes may be involved in the development of UC by regulating the metabolic and immune microenvironment. Finally, regorafenib and R-428 were considered as possible agents for the treatment of UC.

This study offers a novel strategy to early UC diagnosis and treatment by thoroughly characterizing lactylation modifications in UC.

Inflammatory bowel disease (IBD) is a chronic disease that is related to excessive inflammation and an imbalance in the gut microbiota. In this study, the effect of five Bifidobacterium longum subsp. longum strains on alleviating the colitis induced by dextran sulfate sodium (DSS) was investigated. Disease activity index (DAI) scores combined with hematoxylin and eosin (H&E) analysis showed that only B. longum BL300 could significantly alleviate DSS-induced colitis. Furthermore, immunofluorescence analysis confirmed that the expression of the intestinal barrier-related protein ZO-1, occludin, claudin-1 and MUC2 was significantly up-regulated. Moreover, transcriptome analysis of the colon tissue combined with RT-qPCR analysis revealed that levels of pro-inflammatory cytokines IL-2, IL-6, IL-17, TNF-α and IL-1β were decreased and anti-inflammatory cytokine IL-10 level was increased after B. longum BL300 intervention. Notably, the IgA production immune network was activated by B. longum BL300, which eliminated pathogenic bacteria, such as Escherichia, Shigella, Enterobacter and Prosthecobacter, by forming complexes. Meanwhile, the relative abundance of SCFA-producing bacteria was significantly increased. These results highlight the anti-inflammatory effect of B. longum BL300 on DSS-induced colitis, indicating its use as a probiotic candidate to support recovery from ongoing colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease primarily affecting the colon, characterized by mucosal inflammation and ulceration. Monocyte locomotion inhibitory factor (MLIF), a heat-stable pentapeptide derived from Entamoeba histolytica, has demonstrated the anti-inflammatory capacity. The aim of the current work was to test the protective effects of MLIF in a dextran sulfate sodium (DSS)-induced colitis mouse model. Our findings indicated that MLIF significantly inhibition of colitis development, including body weight, DAI score, colon length, and spleen index. MLIF slowing the progression of inflammation in the colon of mice exposed to DSS, evidenced by HE staining and mRNA expression levels of Il1b, Il6, Il18 and Il10. MLIF significantly alleviated intestinal barrier dysfunction in mice exposed to DSS, evidenced by AB-PAS staining and mRNA expression levels of Tjp1, Ocln and Muc2. Importantly, the administration of MLIF in colitis mice exerted beneficial effects on the gut microbiota, enhancing microbial diversity and abundance, and promoting the restoration of gut microbiota homeostasis. Non-targeted metabolomics results suggest that the benefits of MLIF may arise from its modulation of tryptophan metabolism pathways. In conclusion, MLIF prevention inflammation induction and preserves intestinal homeostasis against colitis induced by DSS.

Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease. Glycyrrhiza pallidiflora polysaccharide (GPP) is an important constituent of a species of Glycyrrhiza pallidiflora, but its therapeutic mechanism in UC mice is not clear. A dextran sulphate sodium salt (DSS)-induced mouse model of UC was established, and GPP was extracted by ultrasound-assisted extraction, optimised to a GPP content of 25.66% by one-factor optimisation. The effects of different doses (100, 200, 300 mg/kg) of GPP on UC were investigated. The results showed that GPP could delay the trend of weight loss, reduce the DAI score and decrease colon damage in mice, and GPP had a better ameliorative effect on enteritis, which provided a theoretical basis for studying the effect of natural products on UC.

Rubus chingii Hu (R. chingii) is a valuable edible and medicinal plant. It contains a variety of surprising active compositions. For example, polysaccharides, phenols, terpenes, organic acids, benzenes, and flavonoids. Among them, polysaccharides, as macromolecular compounds, are receiving increasing attention from researchers. Polysaccharides obtained from R. chingii have anti-tumor, anti-colitis, immunomodulatory, anti-obesity, antioxidant and cytoprotective effects. In this paper, the extraction, purification, structural characteristics and health benefits of R. chingii polysaccharides were reviewed, which laid the knowledge foundation and provided the direction for future research. In addition, the structure-activity relationship of R. chingii polysaccharides was analyzed. Its actual and potential applications in the fields of food, pharmaceuticals, and cosmetics have also been discussed. This provides inspiration for the future research and development of its health products and functional foods. In summary, by reviewing the research on R. chingii polysaccharides in recent years, it will help researchers deepen their understanding of them and facilitate further research on R. chingii polysaccharides.

Two series of diarylmethylamine derivatives were synthesized by 1,6-addition reaction between para-quinone methides and 1-methylpiperazine or 2-oxazolidinone, and their structures were identified by 1H NMR,13C NMR and HRMS. In the lipopolysaccharide-induced inflammatory Raw264.7 cells model, 3-CF3 modified active derivative 1l was screened out by inhibiting the excessive production of NO (IC50 = 5.82 μM), and can inhibit the excessive production of ROS. Western blot analyses indicated that 1l can also inhibit the excessive production of pro-inflammatory cytokines (IL-6 and TNF-α) and the nuclear transfer of NF-κB in inflammatory cells. In the dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice model, 1l can effectively inhibit the colonic shortening and suppress inflammatory symptoms of the colonic tissue (HE). Western blot analyses and biochemical indicators demonstrated that 1l can protect the colon of UC mice by regulating the inflammation-related TLR4/NF-κB signaling pathway and the oxidative stress-related Nrf2/HO-1 signaling pathway. Besides, the safety evaluation results of the UC mouse model (serum biochemical indicators, pathological tissue analysis and organ indexes) and the oral acute toxicity test revealed that 1l had certain safety in mice and can resist other tissues damage caused by DSS. In summary, 1l is an effective anti-inflammatory agent that can be developed as a potential drug for treating UC.

Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease characterized by continuous mucosal inflammation confined to the colon and rectum. Although fistulizing complications are a hallmark of Crohn's disease, they are exceedingly rare in UC, which typically involves only the mucosal layer. In these rare instances, however, prolonged and severe mucosal inflammation in UC may lead to deeper tissue injury and the development of transmural complications such as fistulas. This report details a case of a 74-year-old female patient, diagnosed with UC two years ago, who presented to our hospital with abdominal pain, mucoid diarrhea, and a lower left quadrant abdominal abscess. After CT-guided drainage of the abscess, a fistulogram confirmed a salpingo-sigmoidal fistula, with contrast outlining a tract from the sigmoid colon to the left fallopian tube and extending into the endometrial cavity. Due to the infrequency of fistula formation in UC, such a presentation can confuse the diagnosis as it does not conform to the classical pattern of UC. Therefore, this case serves to expand our understanding of the disease process and protect against a premature conclusion that would cause UC to be dismissed as a viable diagnosis when fistula formation is seen on initial presentation.

Ulcerative colitis (UC) is a complex inflammatory condition with limited non-invasive tools to monitor early-stage inflammation. This study aimed to investigate the early stages of inflammation in acute and chronic murine models of dextran sulfate sodium (DSS)-induced colitis using in vivo and ex vivo chemiluminescence imaging.

Two DSS-induced colitis models were used: an acute model over 7 days and a chronic model over 6 weeks. Body weight, stool consistency, and fecal occult blood (FOB) tests were monitored. Chemiluminescence imaging was used to assess inflammation in vivo and ex vivo, complemented by colonoscopy in the chronic model.

In the acute model, DSS-treated mice exhibited weight loss, colon shortening, and positive FOB tests by day 7. Ex vivo chemiluminescence signals exhibited a significant increase as early as day 5 (p < 0.001), while in vivo imaging showed minimal changes. In the chronic model, periodic DSS exposure resulted in recurrent inflammation, with positive FOB tests and significantly elevated ex vivo and in vivo chemiluminescence signals during the final DSS cycle (p < 0.05). Colonoscopy confirmed inflammation progression.

This study demonstrates the progression of inflammation in acute and chronic colitis models. However, in vivo chemiluminescence imaging did not reliably detect the onset of inflammation, limiting its application for early-stage disease detection. Ex vivo chemiluminescence and FOB tests provided more consistent insights into inflammation dynamics, addressing the need for improved non-invasive monitoring tools in UC research.

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder distinguished by alternating phases of remission and exacerbation. Restoring immune balance through the modulation of M1 macrophage polarization represents a potentially valuable therapeutic strategy for UC. Indoleamine 2,3-dioxygenase-1 (IDO1) has been shown to contribute to macrophage plasticity, but its role in the pathogenesis of UC via regulating M1 macrophage polarization has not been studied yet. For the clinical component, we analyzed IDO1 expression in UC using bioinformatics analysis of Gene Expression Omnibus (GEO) datasets and validated the result using western blotting of colonic tissues from new recruited UC patients. Colitis was induced in mice via dextran sulfate sodium (DSS) treatment and subsequently treated with oral administration of 1-methyl-DL-tryptophan (1-MT), an inhibitor of IDO1 pathway. The results indicated that IDO1 expression was significantly elevated in UC patients and correlated with M1 macrophage polarization observed in both human data and colitis mice. Furthermore, 1-MT markedly ameliorated DSS-induced weight loss, colonic shortening and disease severity via inhibiting IDO1 expression level, downregulating GRP78-XBP1 pathway and reducing M1 proportion. Notably, in vitro study revealed that overexpressing IDO1 in RAW264.7 cells induced macrophage M1 polarization with increased expression levels of GRP78 and XBP1, which was attenuated by 1-MT treatment. Additionally, the catalytic effect exerted by IDO1 overexpression on M1 polarization was neutralized by employing an inhibitor targeting the endoplasmic reticulum (ER) stress pathway. Thus, our findings suggest that IDO1 may promote UC progression by skewing macrophages towards M1 polarization through ER stress-associated GRP78-XBP1 pathway.

Ulcerative colitis (UC) is a widespread incurable chronic inflammation of the colon mucosa. Currently, oral small-molecule medications targeting Janus kinase or sphingosine-1-phosphate and monoclonal antibodies to TNF-α,α4β7 integrins and Ustekinumab are the lines of treatment for UC. Up to 50% of patients either do not react to initial treatment or lose response over time, emphasizing the need for innovative treatment. Mirikizumab, a humanized IgG4-variant monoclonal antibody, binds to subunit p19 of interleukin-23. This systematic review aims to evaluate Mirikizumab compared to placebo in treating moderate-to-severe active UC. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and using the Population, Intervention, Comparison, Outcome, Study design (PICOS) model for inclusion and exclusion criteria, we systematically reviewed the literature. Our inclusion criteria encompassed randomized controlled trials assessing Mirikizumab efficacy in treating UC across demographics. We employed the Cochrane Risk of Bias tool (RoB1) to investigate bias within included studies across its seven domains. The statistical analysis was conducted using Review Manager Version 5 software. Four studies were included, comparing patients treated with mirikizumab to placebo groups. All doses of mirikizumab administered intravenously demonstrated clinical remission, specifically, the 200 mg and 300 mg doses showed significant efficacy, with risk ratios of 4.74 (95% CI [1.43, 15.69]) and 1.82 (95% CI [1.33, 2.50]), respectively. During the maintenance phase of extension trials, symptoms subsided with a subcutaneous 200 mg dose (RR = 1.46, 95% CI [0.47, 4.51], P = 0.51). To conclude, mirikizumab demonstrates significant efficacy in treating UC, substaintially improving clinical, endoscopic, and histological outcomes.

Inflammatory bowel diseases (IBD), including ulcerative colitis, are characterized by chronic inflammation and oxidative stress, necessitating novel therapeutic approaches. This study explores the therapeutic potential of snail mucus derived from snails fed different concentrations of carob (SSCS) and compares its efficacy to aqueous carob extracts (AECS). Both SSCS and AECS are rich in bioactive compounds with potential anti-inflammatory, antioxidant and tissue-regenerative effects.

Snail mucus was found to be rich in collagen and allantoin, which are crucial for tissue repair and cell regeneration, whereas carob extracts contained high levels of phenolics, tannins and flavonoids, contributing to their antioxidant properties. In a rat model of acetic acid-induced ulcerative colitis, pretreatment with SSCS, AECS or sulfasalazine significantly alleviated colonic damage. The SSCS30% group exhibited the strongest protective effects, comparable to sulfasalazine, in reducing mucosal injury, inflammation and immune activation. Biochemical analyses demonstrated that SSCS30% effectively decreased systemic inflammation markers (CRP), pancreatic stress indicators (amylase) and liver enzyme levels (AST, ALT, ALP), while enhancing antioxidant defenses and preserving colonic sulfhydryl content.

These findings underscore the therapeutic potential of snail mucus, particularly from snails fed a 30% carob-enriched diet, as a promising natural therapy for IBD. Its potent anti-inflammatory, antioxidant and tissue-regenerative properties suggest that the use of SSCS30% could serve as an innovative approach for managing ulcerative colitis and other inflammatory disorders. These findings suggest that carob-enriched snail mucus could serve as a complementary therapy for ulcerative colitis patients, though clinical validation remains necessary. While these preclinical results are promising, further clinical studies are needed to validate the therapeutic potential of this natural combination in human ulcerative colitis. © 2025 Society of Chemical Industry.

The interplay between diet, host genetics, microbiota, and immune system has a key role in the pathogenesis of inflammatory bowel disease (IBD). Although the causal pathophysiological mechanisms remain unknown, numerous dietary nutrients have been shown to regulate gut mucosal immune function, being effective in influencing innate or adaptive immunity. Here, we proved that transient receptor potential melastatin 8 (TRPM8), a non-selective cation channel, mediates LPS- evoked Ca2+ influx in macrophages leading to their activation. Additionally, we showed that TRPM8 is selectively blocked by the dietary flavonoid luteolin, which induced a pro-tolerogenic phenotype in pro-inflammatory macrophages. Accordingly, genetic deletion of Trpm8 in macrophages caused a deficit in the activation of pro-inflammatory metabolic and transcriptional reprogramming, leading to reduced production of key pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. The TRPM8 anti-inflammatory effect was found to be dependent on lactate which in turn induces IL-10 gene expression. Adoptive transfer of TRPM8-deficient bone marrow in wild-type mice improved intestinal inflammation in a model of colitis. Accordingly, oral administration of luteolin protected mice against colitis through an impairment in the innate immune response. Our study reveals the potential of targeting TRPM8 through specific nutrient interventions to regulate immune function in sub-clinical scenarios or to treat inflammatory diseases, primarily driven by chronic immune responses, such as IBD.

Dahuang Mudan Decoction is a classic Chinese medicine prescription for treating ulcerative colitis (UC). Previous studies have shown that Dahuang Mudan Decoction has preventive and therapeutic effects on mice with dextran sulfate sodium (DSS) induced colitis.

The objective of this research endeavor was to ascertain the most efficacious synergistic blend of Emodin, Luteolin, and Paeonol, the main active ingredients in Dahuang Mudan Decoction, in alleviating UC. Additionally, it sought to elucidate the underlying therapeutic mechanisms and evaluate the safety of the combined components.

Employing Emodin, Luteolin, and Paeonol as starting materials, the optimal combination was selected by orthogonal design. Basic pharmacodynamics was observed in mouse model of UC induced by DSS. The pathological changes of the colon were observed using hematoxylin and eosin (H&E) staining. The changes of cytokines and proteins related to inflammation and intestinal barrier function were detected by WB, Alcian blue staining, immunofluorescence, immunohistochemistry and related kits. Subsequently, 16S rRNA sequencing was used to observe changes in the intestinal flora. To evaluate the therapeutic effect and potential mechanism of the optimal monomer composition on UC mouse model. Finally, we performed toxicity tests as part of the safety assessment of the combination of the three monomers.

The different combinations of Emodin, Luteolin, and Paeonol alleviated DSS-induced colitis to varying degrees. The ELP5 group (Emodin 5 mg/kg + Luteolin 5 mg/kg + Paeonol 15 mg/kg) and ELP9 group (Emodin 15 mg/kg + Luteolin 15 mg/kg + Paeonol 75 mg/kg) had the most significant mitigation effect on UC mice. Mechanistically, the monomeric composition provides a comprehensive treatment for UC by addressing multiple aspects, including anti-inflammatory and antioxidant effects, repairing the damaged intestinal barrier, restoring the intestinal flora structure, and regulating short-chain fatty acid levels. In addition, the combination of Emodin, Luteolin and Paeonol exhibited a more significant effect on DSS-induced colitis compared to the individual components, indicating a synergistic effect among them. In the single-dose toxicity test, no obvious abnormalities were found in the general state or major organs of the mice. In repeated toxicity tests, it was found that the combined use of three monomers had less effect on organ index, hematology and serum biochemical indexes than that of a single compound. Pathological examination showed that the three monomers had certain toxicity to mouse liver, kidney and lung when used alone and in large doses for a long time, and the toxicity was significantly reduced after combined use.

We have determined the optimal combination of three active ingredients in Dahuang Mudan Decoction to alleviate DSS induced colitis in mice by inhibiting intestinal inflammation and oxidative stress, repairing impaired intestinal barrier function, and regulating intestinal flora disturbance. The results of single administration toxicity test proved the safety of the three monomers combined, and repeated administration toxicity test clarified the safe dose range of the combined administration, and also revealed that the combined therapy exhibited superior safety compared to monotherapy.

To address the core pathological features of intestinal barrier disruption and immune imbalance in ulcerative colitis (UC), we developed a nano-targeted formulation (GGQL nano-preparation) based on berberine, puerarin, baicalin, and glycyrrhizin by combining traditional Chinese medicine (TCM) and nanotechnology in this study. We aimed to investigate whether GGQL nano-preparation could promote M2 macrophage polarization, correct intestinal inflammation, and treat UC.

We used databases to identify M2 macrophage-related gene targets for GGQL nano-preparation in UC. Protein-protein interaction networks, topological analysis, and GO/KEGG enrichment analyses revealed GGQL nano-preparation's potential regulation of macrophage polarization via a specific pathway. We validated this using a dextran sulfate sodium (DSS)-induced UC model in C57BL/6 mice. Parameters assessed included the disease activity index (DAI), colon length, colitis macroscopic damage index (CMDI), spleen index, and pathological changes (via HE staining). Immunohistochemistry detected AMPK-PPAR axis factor changes to determine GGQL nano-preparation's impact on M2 macrophage polarization and intestinal inflammation.

Our analyses suggested the GGQL nano-preparation reduced the DAI, enhanced colon length, improved CMDI scores, and mitigated splenic inflammation. HE staining showed GGQL nano-preparation alleviated inflammation in the spleen, lungs, and colon. Immunohistochemical findings indicated GGQL nano-preparation upregulated AMPK, PPAR, and SIRT1 expression. Mechanistically, GGQL nano-preparation promoted M2 macrophage polarization through the AMPK-PPARγ axis, achieving therapeutic objectives for UC.

The GGQL nano-preparation effectively promotes M2 macrophage polarization via the AMPK-PPARγ axis, treating UC.

Ulcerative colitis (UC), a recurrent chronic colon inflammation, presents substantial therapeutic challenges due to the frequent adverse effects associated with conventional pharmacological treatments. These limitations underscore the critical need for developing alternative dietary interventions with improved safety profiles. The present study investigated the therapeutic potential of Enteromorpha prolifera soluble dietary fiber microparticles (EDFM) in UC management, focusing on restoring mucosal barrier integrity and modulating gut microbiota homeostasis.

EDFM was fabricated through aqueous extraction of E. prolifera soluble dietary fiber via boiling followed by spray-drying. A mouse UC model was induced by dextran sulfate sodium (DSS). The severity of UC was evaluated through daily disease activity index (DAI) scoring; quantification of pro-inflammatory cytokines (TNF-α, IL-1β) via ELISA; histopathological analysis of colon sections with H&E staining; immunofluorescence detection of tight junction proteins (ZO-1, occludin); and 16S rRNA sequencing for gut microbiota.

EDFM treatment significantly reduced the expression of pro-inflammatory cytokines (TNF-α and IL-1β), enhanced the expression of tight junction proteins (ZO-1 and occludin), and stimulated mucin (MUC2) production. Additionally, EDFM promoted the proliferation of beneficial probiotics (Alloprevotella, Lachnospiraceae_NK4A136_group, and Ruminococcaceae_UCG-014), while inhibiting pathogenic bacteria (Escherichia-Shigella, Parabacteroides, Rikenellaceae_RC9_gut_group, Odoribacter, and [Ruminococcus]_torques_group).

EDFM supplementation significantly ameliorates UC through dual modulation of gut microbiota and intestinal barrier integrity, indicating its potential as a functional food ingredient for UC prevention and treatment.

Ulcerative colitis (UC) is a recurrent, chronic disease whose main symptoms include weight loss, diarrhea, and blood in the stool. In recent years, the incidence of UC has been increasing year by year, which seriously affects the daily life of patients. Luteolin (Lut), as a flavonoid, is widely found in a variety of vegetables and fruits and has been shown to have a variety of pharmacological activities. This work investigated the effects of Lut on dextrose sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice, with a special focus on the role of endoplasmic reticulum (ER) stress in this. The outcomes demonstrated that colitis symptoms, including disease phenotype, elevated inflammatory factor levels, intestinal barrier damage, and gut microbiota disruption, were considerably alleviated in UC model mice treated with luteolin. Also, Lut alleviated ER stress and apoptosis in UC mice. We then explored the effects of Lut on ER stress and apoptosis induced by thapsigargin (TG) and tunicamycin (TM) in HT29 cells in vitro. It was found that Lut treatment inhibited TM/TG-induced ER stress and apoptosis. However, these inhibitory effects of Lut were attenuated by SIRT1 silencing in TM-treated HT29 cells. In conclusion, our results suggest that Lut supplementation in a mouse model of colitis improves the symptoms of colitis in mice, which provides a theoretical basis for further application of Lut in the prevention of inflammation-related diseases in humans.

We detect and interactively visualize occurrence, frequency, sequence, and clustering of extraintestinal manifestations (EIM) and associated immune disorders (AID) in 30,334 inflammatory bowel disease (IBD) patients (Crohn's disease (CD) n = 15924, ulcerative colitis (UC) n = 11718, IBD unclassified, IBD-U n = 2692, 52% female, median age 40 years (IQR: 25)) with artificial intelligence (AI). 57% (CD > UC 60% vs. 54%, p < 0.00001) had one or more EIM and/or AID. Mental, musculoskeletal and genitourinary disorders were most frequently associated with IBD: 18% (CD vs. UC 19% vs. 16%, p < 0.00001), 17% (CD vs. UC 20% vs. 15%, p < 0.00001) and 11% (CD vs. UC 13% vs. 9%, p < 0.00001), respectively. AI detected 4 vs. 5 vs. 5 distinct EIM/AID communities with 420 vs. 396 vs. 467 nodes and 11,492 vs. 9116 vs. 16,807 edges (links) in CD vs. UC vs. IBD, respectively. Our newly developed interactive free web app shows previously unknown communities, relationships, and temporal patterns-the diseasome and interactome.

Inflammatory bowel disease (IBD) significantly impacts employment and work productivity, necessitating support for balancing work and treatment (SBWT). While SBWT systems have been formalized in Japan, awareness among healthcare professionals remains low. This study aimed to evaluate the effectiveness of an educational program on SBWT for healthcare professionals in Hokkaido, Japan.

A 2-year questionnaire-based study was conducted across eight medical facilities in Hokkaido, Japan, from November 2022 to November 2024. The educational program, comprising lecture-based and self-directed learning formats, addressed six key components of SBWT. Pre- and post-program surveys assessed changes in awareness, interest, and behaviors related to SBWT.

Pre-program awareness of SBWT was low (36.7% among doctors, 28.2% among medical staff). Post-program, awareness increased significantly to 81.3% and 58.3%, respectively (p < 0.01). Interest in SBWT improved across several categories for both groups, with greater gains among medical staff. Behavioral changes, such as detailed employment-related consultations with IBD patients and improved reporting practices from medical staff to doctors, were observed but not statistically significant. Lecture-based learning was more effective than self-directed methods, in increasing awareness, interest, and engagement with SBWT, particularly for medical staff.

The educational program successfully enhanced awareness and interest in SBWT, with lecture-based methods proving more effective for medical staff. These findings emphasize the need for tailored educational strategies based on baseline knowledge. Future initiatives should focus on sustaining knowledge acquisition, expanding programs nationwide, and assessing long-term impacts on healthcare practices and patient outcomes.