Mirikizumab, approved for the treatment of moderately to severely active ulcerative colitis (UC), may be prescribed in a similar placement to ustekinumab in second-line settings. Payers may compare the economic value when making formulary decisions. This study estimated and compared the cost per remission of the second-line therapies mirikizumab versus ustekinumab in patients with UC.

An Excel-based analytic model was developed to estimate the cost per additional patient achieving clinical remission at the end of one year in biologic/Janus kinase inhibitor (JAKi)-experienced patients (second-line therapy) with UC from a United States commercial payer perspective. A network meta-analysis of published pivotal randomized clinical trials was used to derive the number needed to treat (NNT) for clinical response, clinical remission, and endoscopic remission/endoscopic improvement/mucosal healing for ustekinumab and mirikizumab in the study population. The model included the treatment cost (wholesale acquisition costs [WAC] and treatment administration costs) during the induction and maintenance phases. A scenario involving the availability of a ustekinumab biosimilar was also evaluated, assuming the NNT remained the same as ustekinumab but with a WAC set at 50% lower than its current WAC.

The costs per patient achieving clinical remission for mirikizumab vs. ustekinumab as a second-line therapy were $461,096 vs. $67,273 during induction and $501,456 vs. $1,079,189 during maintenance. The cost per clinical remission in case of dose escalation during maintenance was lower for mirikizumab vs. ustekinumab ($501,456 vs. $1,569,127). Considering the ustekinumab 130 mg IV biosimilar, the scenario resulted in a lower cost per clinical remission for mirikizumab vs. a ustekinumab biosimilar during the maintenance phase ($501,456 vs. $539,594).

Mirikizumab is projected to have a lower cost per remission during maintenance therapy than ustekinumab. Given the need for long-term treatment for this chronic condition, mirikizumab appears to be a cost-efficient treatment option.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease for which remission is dependent on corticosteroid (CS) treatment. The diversity of disease pathophysiology necessitates optimal case-specific treatment selection. This study aimed to identify prognostic factors for refractory UC using a machine learning model based on nationwide registry data.

The study included 4003 patients with UC with a Mayo score of ≥3 at the time of registration who had been using CS since their entry out of 79,096 newly registered UC cases in a nationwide registry from April 2003 to March 2012 (before the widespread use of biologic agents in Japan) with 3-year data. A pointwise linear (PWL) model was used for machine learning.

A PWL model, which was developed to predict long-term remission (lasting >3 years), had an area-under-the-curve (AUC), precision rate, recall rate, and F-value of 0.774, 0.55, 0.70, 0.62, respectively, in the test dataset from the time of registration to 2 years later. Furthermore, the presence of pseudopolyps at the time of registration was significantly and negatively correlated with remission, highlighting its importance as a prognostic factor.

In this study, we constructed a highly accurate prognosis prediction model for UC, in which inflammation persists for an extensive period, by training a machine learning model for long-term disease progression. The results showed that machine learning can be used to determine the factors affecting remission during the treatment of refractory UC.

Probiotics emerges as a promising option for ulcerative colitis (UC) treatment, but its application remains challenging due to insufficient colon-targeted delivery efficiency and survival against the inflammation-associated intestinal oxidative stress. To address these issues, here we report a supramolecular liposome-microgel complex (SLMC) incorporated with Bacillus subtilis spores (BSSs) and dexamethasone (DEX) for orally-deliverable probiotic UC therapy. Specifically, BSSs and cholesterols were conjugated with gelatin via diselenide ligation to prepare microgels, followed by supramolecular complexation with UC-targeted DEX-loaded liposome via microfluidic engineering. The orally-administered SLMC efficiently accumulated in UC-affected colonic sites to release BSSs and DEX. DEX elicited rapid anti-inflammatory effect to reduce ROS generation, which cooperated with the ROS consumption by spore germination and diselenide cleavage to orchestrate an anaerobic intestinal microenvironment, thus promoting Bacillus subtilis colonization to restore gut homeostasis and initiate anti-inflammatory microbiota-macrophage metabolic crosstalk. Indeed, in vivo analysis showed that the SLMC treatment markedly inhibited pro-inflammatory TLR4-NF-κB signaling activities in mucosal macrophages through localized DEX delivery and boosting tryptophan metabolite production, leading to robust and durable UC abolishment. This study offers a practical approach for improving UC treatment in the clinic.

MCPA-Na (2-methyl-4-chlorophenoxyacetic acid) is a selective herbicide widely used in agricultural cultivation. Despite monitoring indicating risks to aquatic life, the specific organ effects and pathogen susceptibility are unclear. Therefore, we constructed a "compound-core target-signaling pathway" network using network toxicology methods, and the results showed that MCPA-Na interacted with multiple organs of loach (including intestine, liver, kidney, heart, gills, skin and blood). STRING and Cytoscape software were used to screen the core targets: PPAR (Peroxisome proliferator-activated receptor), ACE (angiotensin converting enzyme), REN (Renin), and CA9 (carbonic anhydrase). KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis showed that the core targets of each tissue were significantly enriched in the renin-angiotensin system, NF-κB signaling pathway, adherens junctions and cholinergic synapses. The relationship between the toxicology and molecular markers of MCPA-Na was further explored by using animal experiments, and the susceptibility of Misgurnus anguillicaudatus (loach) to opportunistic pathogens after toxic exposure was simulated by using opportunistic pathogen challenge Aeromonas hydrophila (A. hydrophila). It was found that the compound induced oxidative stress and triggered intestinal inflammation and promoted apoptosis. These processes undermine the intestinal barrier and increase the susceptibility of loach to the A. hydrophila, thereby exacerbating the challenge of aquaculture food safety.

Activation of NOD-like receptor protein 3 (NLRP3) can lead to the production of inflammatory factors and perturbation of macrophage polarization, leading to an intestinal immune imbalance that promotes the progression of ulcerative colitis (UC). In this study, we investigated the therapeutic effect of Kurarinone and Nor-kurarinone on UC and their regulatory mechanisms relating to NLRP3 inflammasome activation and macrophage polarization. UC mice were induced using dextran sulfate sodium (DSS) and treated with Kurarinone and Nor-kurarinone. Results showed that Kurarinone and Nor-kurarinone could alleviate weight loss, decrease the disease activity index (DAI) score, shorten colon length, inhibit formation of the NLRP3 inflammasome in the colon and regulate macrophage polarization in UC mice. The THP-1 cells were used as an in vitro model of the NLRP3 inflammasome, conducted by treatment with lipopolysaccharide (LPS) and ATP/Nigericin. Kurarinone and Nor-kurarinone can inhibit the NLRP3 inflammasome formation response by disrupting the NLRP3/ASC interaction to inhibit NLRP3 assembly and then regulating the polarization of macrophages. In conclusion, Kurarinone and Nor-kurarinone inhibited NLRP3 inflammasome assembly to counteract activation of the NLRP3 inflammasome. This inhibition led to a reduction in M1 polarization of intestinal macrophages in UC mice to keep the balance of M1/ M2 macrophages. Our study suggests that Kurarinone and Nor-kurarinone may be novel therapeutic modalities for UC.

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by the overproduction of reactive oxygen species (ROS) and the release of inflammatory mediators. Dihydroartemisinin (DHA) is a semi-synthetic active metabolite of artemisinin that has anti-inflammatory, antioxidant, and anti-fibrotic properties.

This study aimed to assess the therapeutic benefits of DHA on acetic acid(AA) -induced UC in rats, with particular emphasis on its anti-inflammatory effects and its influence on NFκB/TNF-α/RIPK1 necroptotic pathways.

Eighteen rats were allocated into control, acetic acid-induced colitis (AA), and DHA-treated (AA+DHA) groups. Colitis was caused by rectal instillation of 5 % acetic acid. DHA was supplied via intraperitoneal injection. Histological, biochemical studies of oxidative stress, inflammatory and anti-inflammatory mediators, Western blotting for TNF-α, RIPK1, and caspase 3, and immunohistochemical assessment of NFκB, TNF-α, and RIPK1, were conducted.

DHA treatment markedly diminished macroscopic damage, disease activity index, histopathology scores, and malondialdehyde (MDA) levels, enhancing glutathione (GSH) levels. Additionally, DHA decreased serum TNF-α and IL-6 and increased IL-10. Western blotting and immunohistochemistry investigations validated the reduced expression of TNF-α, RIPK1, and caspase 3 in DHA-treated rats.

DHA demonstrates protective properties against acetic acid-induced UC by decreasing oxidative stress and inflammation, modifying TNF-α activity to regulate apoptotic and necroptotic pathways. So, DHA may be a favorable therapeutic alternative for the management of ulcerative colitis.

The U-ACTIVATE long-term extension study aims to evaluate the long-term efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis. Here, we report interim results after 3 years of total treatment.

U-ACTIVATE is an ongoing, 288-week, phase 3, long-term extension study done at 307 centres across 43 countries (active sites on Dec 31, 2021, are presented as part of this interim analysis) and began on Jan 31, 2017. In brief, patients aged 16-75 years with a confirmed diagnosis of moderately to severely active ulcerative colitis for 90 days or more, an adapted Mayo score of 5-9, and an endoscopic subscore of 2 or 3 were eligible for the upadacitinib induction studies; patients who had a clinical response in the induction studies were eligible to enter the U-ACHIEVE maintenance study. Individuals who completed the U-ACHIEVE maintenance study were subsequently eligible for inclusion in the efficacy population of this long-term extension study. Patients in clinical remission per adapted Mayo score at week 52 of the maintenance study could continue their double-masked treatment upon entering the long-term extension study. Patients not in clinical remission originally randomly assigned to upadacitinib 15 mg were eligible to escalate to upadacitinib 30 mg, those originally randomly assigned to upadacitinib 30 mg continued on upadacitinib 30 mg, and those originally assigned to placebo were eligible to escalate to upadacitinib 15 mg in a masked way. We present data from weeks 48 and 96 of the long-term extension period. Key efficacy outcomes were clinical remission (per adapted Mayo score), endoscopic remission, maintenance of clinical remission, and maintenance of endoscopic remission, and are presented for those patients who had a clinical response after 8 weeks of upadacitinib 45 mg induction, completed 52 weeks of maintenance (U-ACHIEVE maintenance), and subsequently entered the long-term extension. Safety outcomes were treatment-emergent adverse events and adverse events of special interest, which were prespecified and were recorded in two populations: one comprising patients who received at least one dose of study drug in the long-term extension study and the other comprising all patients in the maintenance or long-term extension studies. Our primary approach for efficacy analysis was as-observed (ie, all observed data were used without imputation for missing data until patients switched to a different dose during the long-term extension study). This study is registered with ClinicalTrials.gov (NCT03006068).

414 patients from the phase 3 upadacitinib U-ACHIEVE maintenance study were eligible to enter this long-term extension study for assessment of efficacy endpoints following treatment with upadacitinib. Of these individuals, 369 patients (231 [63%] male individuals and 138 [37%] female individuals) were treated with upadacitinib in the long-term extension study: 142 patients with upadacitinib 15 mg and 227 with upadacitinib 30 mg. In the as-observed population, 84 (71%) of 118 patients receiving upadacitinib 15 mg were in clinical remission at week 48, as were 130 (67%) of 193 receiving upadacitinib 30 mg; by week 96, 69 (76%) of 91 patients receiving upadacitinib 15 mg and 104 (74%) of 141 of those receiving upadacitinib 30 mg were in clinical remission. Most patients who entered the long-term extension in clinical remission maintained it in the as-observed analysis (week 48 upadacitinib 15 mg 62 [81%] of 77 and upadacitinib 30 mg 90 [81%] of 111; week 96 upadacitinib 15 mg 50 [78%] of 64 and upadacitinib 30 mg 69 [84%] of 82). In the as-observed population, 60 (49%) of 123 patients receiving upadacitinib 15 mg and 93 (46%) of 202 receiving upadacitinib 30 mg were in endoscopic remission at week 48; by week 96, 45 (47%) of 95 patients receiving upadacitinib 15 mg and 69 (45%) of 153 receiving upadacitinib 30 mg were in endoscopic remission. Most patients who entered the long-term extension in endoscopic remission maintained it in the as-observed analysis (week 48 upadacitinib 15 mg 28 [70%] of 40 and upadacitinib 30 mg 51 [76%] of 67; week 96 upadacitinib 15 mg 20 [65%] of 31 and upadacitinib 30 mg 37 [73%] of 51). In the long-term extension-only safety analysis, we assessed data from 467 patients, representing 1027·9 patient-years of continuous long-term extension exposure on a consistent upadacitinib dose. Treatment-emergent adverse events were recorded at 238·5 events per 100 patient-years for upadacitinib 15 mg and 233·4 events per 100 patient-years for upadacitinib 30 mg. Event rates of serious treatment-emergent adverse events were 11·7 events per 100 patient-years for upadacitinib 15 mg and 12·4 events per 100 patient-years for upadacitinib 30 mg. The most common adverse events of special interest were hepatic disorder, lymphopenia, creatine phosphokinase elevation, serious infection, neutropenia, and herpes zoster. Three treatment-emergent adverse events leading to death were reported in the long-term extension-only safety population.

This interim analysis supports the positive long-term risk-benefit profile for upadacitinib 15 mg and 30 mg among patients with moderately to severely active ulcerative colitis.

AbbVie.

Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the intestinal mucosa, with predominant localization in the colon in ulcerative colitis (UC) or affecting the entire length of the gastrointestinal tract in Crohn's disease (CD). Recent advances in the drug development space have been marked by a return to orally administered small molecules with novel mechanisms of action such as Janus kinase inhibitors. Additionally, the prevalence of certain chronic conditions is higher in IBD patients, many of which are treated with orally administered drugs. Given the pathophysiology and localization of IBD, altered drug absorption from the gastrointestinal tract can be expected. This review discusses several physiological differences between the small and large intestine with the potential to influence drug absorption including pathophysiology related alterations associated with IBD. The main physiological parameters which are identified include luminal fluid volume, luminal pH, transit time, bile salt concentration, microbiome, absorptive surface area, permeability and metabolizing enzymes and transporters. Literature regarding these factors in IBD patients is marked with high heterogeneity in reporting of disease severity and location leading to difficulties in interpreting data across different studies. While the influence of most of these factors has been directly assessed in healthy volunteers, this is rarely the case for IBD patients. Furthermore, studies which used PBPK modelling to describe the PK of an orally administered drug in an IBD population and were able to verify their findings using clinical data are critically examined. These models were able to incorporate the pathophysiological changes associated with IBD and partly succeeded in adequately predicting drug absorption in this population. Given the limited amount of PBPK studies performed on a limited number of drugs, the developed models are most likely not suitable to be used as a general PBPK model for the IBD population.

Ferroptosis in colonic epithelial cells has been implicated in the development of ulcerative colitis (UC) and the accompanying gut leakage. Scutellaria baicalensis Georgi (Scu) is widely used herb medicine for alleviating UC.

We aimed to clarify the therapeutic effect of Scu on UC by inhibiting intestinal epithelial cell ferroptosis and explore its regulatory mechanisms on lipid peroxidation and the GPX4/ACSL4 pathways.

UPLC-Q-TOF/MS was employed to analyze chemicals in the herbal extract and the colonic exposure of prototypes in Scu-treated mice. Additionally, the main compounds were quantified using HPLC-UV. The ameliorative effects of Scu were comprehensively explored in a UC mouse model established by feeding with dextran sulfate sodium (DSS). HPLC-MS based metabolomic studies were conducted to identify the differential metabolites in colon tissues from Scu or vehicle treated UC mice. Network pharmacology was conducted for target prediction and potential pathway analysis. In conjunction with these bioinformatic analyses, we performed RT-qPCR, immunofluorescence, immunohistochemistry and immunoblotting to elucidate the regulatory mechanisms of Scu on ferroptosis-related pathways in both in vivo and in vitro models.

78 chemical constituents in Scu were characterized, with 42 detected in the colonic tissues of Scu-treated mice. Scu could alleviate UC related symptoms in mice, including increased colon length and decreased pathological score. Furthermore, Scu inhibited pro-inflammatory cytokines and mediators, while improving gut barrier function by increasing the expression of ZO-1 and Occludin at both mRNA and protein levels. Based on metabolomic studies, a total of 71 differential metabolites exhibited a reversal trend following Scu administration. These findings, combined with results from network pharmacology, suggest that arachidonic acid (AA) metabolism and ferroptosis may serve as potential pathways for Scu intervention in UC. Further experiments indicated that the amelioratory actions of Scu on ferroptosis partially contributed to its modulation on lipid peroxidation and its regulatory influence on the GPX4/ASCL4 axis to ameliorate UC. When AA was administered at the same time as concurrently with Scu, the regulatory effects of Scu on ferroptosis, GPX4/ASCL4 axis, and its protective effects against UC were significantly reduced. Moreover, the inhibitory effect of Scu on ferroptosis was weakened when we knocked down GPX4 or overexpressed ACSL4 in vitro.

The ameliorative effect of Scu in UC is closely related to the regulation of lipid peroxidation and GPX4/ASCL4 mediated intestinal epithelial ferroptosis.

Etrasimod is a synthetic, non-biological, orally administered small molecule sphingosine-1-phosphate receptor (S1PR) modulator. Etrasimod was approved by the Food and Drug Administration in 2023 and by the European Medicine Agency in 2024, constituting a new therapeutic option for the treatment of moderately to severely active ulcerative colitis in patients 16 years of age and older in the European Union. Its efficacy and tolerability have been demonstrated in several clinical trials both as induction and maintenance treatment, as well as in long-term extension studies. This article reviews the pharmacodynamic characteristics of etrasimod, its main differences with biological drugs and other small molecules (janus kinases inhibitors), as well as its clinical efficacy including certain subpopulations such as patients with isolated ulcerative proctitis, and the impact on their quality of life.

In randomised controlled trials, mirikizumab achieved clinical remission and improved outcomes of patients with moderate to severe ulcerative colitis (UC). However, there is currently no real-world evidence for mirikizumab.

To evaluate the real-world effectiveness and safety of mirikizumab.

In a retrospective cohort study among three facilities, we included patients with UC who first received mirikizumab between June 2023 and April 2024. The primary outcome was the change in the partial Mayo score (PMS) from week 0 to 12. Secondary outcomes included changes in serum C-reactive protein (CRP) and leucine-rich α2-glycoprotein (LRG) levels from week 0 to 12; clinical remission rate (PMS < 2 with rectal bleeding subscore of 0), CRP remission rate (< 3.0 mg/L), and LRG remission rate (< 12.7 μg/mL) at week 12; and adverse events during induction therapy.

We included 52 patients. Median (interquartile range) PMS decreased from week 0 to 12 (5 [3-6] to 2 [0-3], p < 0.001). CRP and LRG levels also decreased (CRP: 3.8 [0.9-7.3] to 1.8 [0.5-4.0] mg/L, p = 0.015; LRG: 20.1 [16.3-23.2] to 15.9 [12.8-23.2] μg/mL, p = 0.014). Rates of clinical remission, CRP remission, and LRG remission at week 12 were 44.2%, 67.3%, and 27.3%, respectively. There were no adverse events leading to permanent discontinuation of mirikizumab or death.

This real-world study demonstrated the short-term effectiveness and safety of mirikizumab in patients with UC.

Midbrain astrocyte-derived neurotrophic factor (MANF) is a secreted protein induced by endoplasmic reticulum stress. Previous studies have indicated that intravenous administration of 1 mg/kg/day recombinant human MANF protein with His tag (His-MANF) for 3 days can ameliorate acute ulcerative colitis in mice. However, long-term intravenous therapy has many disadvantages. In this paper, His-MANF protein was successfully encapsulated into alginate and hyaluronic acid hybrid hydrogel microcapsules in one step using the gas shear method and then coated by Eudragit S100 to construct an oral colon-targeted delivery system (MSH@E). The MSH@E microcapsules exhibited controlled and sustained release behavior and colon-targeting properties. Both fluorescent imaging and immunohistochemistry staining results showed that His-MANF protein could accumulate in the colitis colon for a longer residence time after oral delivery. In vivo studies demonstrated that oral administration of MSH@E microcapsules could alleviate DSS-induced colitis in mice without systemic toxicity. Importantly, even if the oral His-MANF dose was half of the intravenous His-MANF dose, oral delivery was still much more effective than intravenous injection, suggesting the development of the oral colon-targeted delivery system (MSH@E) has great significance and makes a breakthrough from intravenous to oral administration for His-MANF treatment of ulcerative colitis (UC).

Globally, the incidence and prevalence rates of ulcerative colitis (UC) show a rising pattern. The limited efficacy and significant adverse effects associated with current treatment options underscore the need for novel therapeutic approaches. It has been found that linagliptin, a dipeptidyl peptidase-4 inhibitor, activates AMPK in different disease conditions. The main objective of the present work was to elucidate the potential implications of the AMPK/FOXO3a mediated by linagliptin in rats with chronic colitis. The findings of the current report revealed the first robust in-vivo evidence advocating the coloprotective effect of linagliptin against dextran sodium sulfate-induced chronic UC in rats. It has demonstrated potential beyond its antidiabetic effects by modulating FOXO3a localization. By shifting FOXO3a from the cytosol to the nucleus, linagliptin enhanced the transcription of genes involved in attenuation of pro-inflammatory events and restoration of redox homeostasis. Nuclear FOXO3a also impacted NFκB activity, reducing inflammation. This conclusion was fundamentally supported by the documented improvements in histopathological changes evidenced by reduced inflammation, edema, crypt atrophy, and submucosal fibrosis. Moreover, decreased colon weight/length ratio, as well as reduced scores of disease activity and macroscopic damage indices, were observed. Furthermore, it corrected body weight loss during the time frame of the experiment. These findings underscore the anti-inflammatory potential of therapies that promote the nuclear localization of FOXO3a in inflammatory conditions. Linagliptin's ability to modulate FOXO3a localization might be particularly useful for diabetic patients suffering from inflammatory bowel diseases. However, further molecular investigations are required to validate the findings and to assess the clinical application of this approach as a valid tool for alleviating UC.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by impaired intestinal mucosal barrier function, leading to persistent inflammation and tissue damage. Current therapies often fail to address barrier dysfunction, highlighting the need for innovative treatments. This study developed a novel therapeutic strategy by combining decellularized porcine small intestinal submucosa (D-SIS) with fibroblast growth factor 20 (FGF-20) to promote mucosal repair and restore barrier integrity in a TNBS-induced colitis rat model. The D-SIS-based hydrogel, supplemented with hyaluronic acid (HA), was designed to enhance FGF-20 stability and enable sustained drug release. Results showed that the FGF-20-loaded hydrogel (MAF) exhibited excellent rheological properties, erosion resistance, and controlled drug release, making it suitable for rectal administration. In vitro cell experiments demonstrated that MAF enhanced Caco-2 cell proliferation, migration, and tight junction protein expression, restoring epithelial barrier integrity. In the colitis model, MAF significantly reduced disease activity index (DAI) scores, attenuated inflammation, and restored mucosal morphology. Additionally, MAF promoted goblet cell regeneration, enhanced mucus secretion, and upregulated intestinal stem cell markers, indicating its ability to repair both epithelial and mucus barriers. In conclusion, the MAF hydrogel represents a promising therapeutic approach for UC by combining the regenerative properties of FGF-20 with the bioactive support of D-SIS.

Ulcerative colitis (UC) is a persistent intestinal disorder featuring periodic flare-ups of the colon's inner lining inflammation. Current therapeutic strategies, while effective in managing symptoms, are often limited by side effects and high costs. This study investigates the potential of pectin-loaded ferulic acid (PC-FA) nanoparticles as a novel therapeutic approach for UC, focusing on their ability to modulate the cGAS-STING pathway, a key mediator in the inflammation associated with UC. PC-FA nanoparticles were prepared and characterized for their physicochemical properties, antioxidant capacity, biocompatibility, and influence on the cGAS-STING pathway. In vitro experiments demonstrated that PC-FA nanoparticles enhanced the solubility and bioavailability of ferulic acid (FA), reduced oxidative stress, and protected colon epithelial cells from damage caused by the administration of dextran sulfate sodium (DSS). In vivo studies in a DSS-induced colitis mouse model showed that PC-FA nanoparticles mitigated weight reduction, lowered disease activity index (DAI) scores, and sustained colon length, and ameliorated histopathological changes. Additionally, PC-FA nanoparticles effectively targeted DNA damage and inhibited the cGAS-STING pathway, leading to a significant reduction in pro-inflammatory cytokines. Pharmacokinetic studies revealed rapid absorption of PC-FA in the bloodstream, with a predominant distribution in the intestines. The study concludes that PC-FA nanoparticles are a promising therapeutic strategy for UC, offering targeted drug delivery, enhanced bioavailability, and anti-inflammatory effects.

Inflammatory bowel diseases (IBD) have been associated with an increased long-term risk of coronary artery disease due to chronic systemic inflammation.

To evaluate the risk of major adverse cardiovascular events (MACE) after coronary interventions.

In this nationwide cohort study of adults undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) (2012-2022), patients with IBD were propensity score-matched 1:10 to comparators without IBD. The primary outcome was MACE, a composite of acute myocardial infarction, stroke, hospitalisation for heart failure, or mortality. Secondary outcomes included each MACE component, 30-day all-cause readmission, revascularisation and in-hospital outcomes including intensive care unit admission and length of hospital stay. We calculated hazard ratios (HRs) and incidence rates (IRs) using Cox proportional hazards modelling.

We included 987 patients with IBD and 9571 matched comparators. After a median follow-up of 3.5 years, MACE occurred in 488 patients with IBD (49.4%, IR: 96.5/10,000 person-years [PY]) and in 3857 matched comparators (40.3%, IR: 68.9/10,000 PY); HR 1.37 (95% CI, 1.24-1.52). This equates to one additional MACE for every 36 patients with IBD over 10 years. The risk of each MACE component was increased, except for stroke. There were no differences between IBD subtypes or coronary intervention (PCI vs. CABG). Risks were highest in older individuals and elective interventions.

Patients with IBD were at 37% higher risk of MACE after coronary intervention, indicating a need for intensified cardiovascular risk reduction in these high-risk individuals.

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), a persistent immune-mediated disorder lacking effective treatment, is distinguished by gut microbiota dysbiosis, abnormal activation of the NLRP3 inflammasome pathway, and apoptosis. Despite growing attention to these factors, understanding their significance in UC pathogenesis remains a challenge. The present study explores the potential therapeutic impact of Bacillus clausii (Bc) spores in a murine UC model induced by drinking 4 % (w/v) dextran sulfate sodium (DSS) in C57BL/6 mice. Subsequently, the DSS-induced mice were orally administered either Bc at varying concentrations (105 and 1010 Colony forming unit, CFU) or sulfasalazine (SSZ) at a dosage of 200 mg/kg for 7 days. The disease-specific activity index (DAI) was calculated daily utilizing parameters such as body weight, diarrhea, and bloody stool. Changes in fecal Firmicutes and Bacteroidetes abundance, colonic TXNIP and NLRP3 contents, as well as colonic caspase-1, IL-1β, Bax, and Bcl-2 expression, were investigated. Additionally, markers related to oxidative stress and inflammation, histopathological changes and caspase-3 immunohistochemistry testing were conducted. DSS-treated mice had significantly higher DAI scores compared to controls, indicating severe colitis. However, SSZ treatment or Bc (105 CFU) dramatically lowered DAI scores, with the highest Bc dosage (1010 CFU) producing the greatest improvement. Furthermore, Bc (1010 CFU) substantially (p < 0.05) boosted fecal Firmicutes while decreased Bacteroidetes, indicating reversal of gut dysbiosis. Bc effectively reduced colonic oxidative stress and inflammation by replenishing GSH and catalase and modulating the NF-κB, Nrf2/HO-1, and TXNIP/NLRP3 pathways. Additionally, Bc (1010 CFU) exhibited histologically almost normal mucosa, with maintained architecture and reduced apoptosis, as seen by normalization of Bcl2 and Bax with decreased caspase-3. Collectively, these findings point to the potential usefulness of Bc spores in preventing and treating DSS-induced colitis, positioning them as a promising candidate for UC management.

Inflammatory bowel disease (IBD) remains an incurable condition, often accompanied by high rates of anxiety and depression, further diminishing the quality of life of patients. Endogenous gasotransmitters, such as carbon monoxide (CO) and hydrogen sulfide (H₂S), exhibit potent anti-inflammatory and immunomodulatory effects. However, their therapeutic application is limited by challenges in targeted delivery to affected tissues. Here, we propose a novel strategy for targeted gut delivery of CO/H2S through engineering Escherichia coli Nissle 1917 (EcN) with CO/H2S-releasing copolymer (POSR) loading. This engineered probiotic (POSR@EcN) enhances EcN colonization in the intestine and enables controlled, localized release of CO/H2S at inflamed sites. The release of CO/H2S modulates inflammation, restores intestinal barrier integrity, and reshapes gut microbiota by promoting beneficial bacteria and increasing short-chain fatty acids production, effectively alleviating IBD symptoms. Notably, targeted CO/H2S delivery also elevates neuroprotective metabolites like indoleacetic acid and γ-aminobutyric acid, reducing neuroinflammation via the gut-brain axis and mitigating anxiety- and depression-like behaviors in IBD mice. This approach highlights the potential of EcN as a probiotic carrier for the targeted delivery of gasotransmitters, offering a promising strategy for IBD treatment.

Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals widely used in industrial and consumer products, leading to environmental contamination and human exposure. This review focuses on perfluoroalkyl acids, a subset of PFAS, which are primarily encountered through diet, including drinking water, and other pathways such as dust ingestion, and dermal contact. Impaired vaccine antibody response has been identified as the most critical effect for risk assessment by the European Food Safety Authority. Furthermore, human epidemiological studies have linked exposure to certain PFAS to various immune-related outcomes, such as asthma, allergies, and inflammatory bowel disease. This review examines potential immunomodulatory effects of perfluoroalkyl acids at the primary sites of exposure: lungs, intestines, and skin, using human epidemiological data as the basis for investigating these impacts. While animal studies are referenced for context, this paper highlights the need for further human-based research to address key questions about PFAS and their immunological impacts. The state of in vitro toxicity testing related to these effects is thoroughly reviewed and critical issues pertaining to this topic are discussed.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon. The specific cause of UC is still not fully understood, but this condition is believed to arise from a combination of environmental, genetic, microbial, and immune factors. This study aimed to explore the specific roles of macrophages and fibroblasts in UC pathogenesis, focusing on their interactions and contributions to disease progression.

We utilized single-cell RNA sequencing (scRNA-seq) to analyze macrophages and fibroblasts in peripheral blood and colon biopsy samples from UC patients. Bulk RNA sequencing and spatial transcriptomic data from the Gene Expression Omnibus (GEO) database and flow cytometry and multiplex immunohistochemistry (mIHC) data were used for validation. Statistical analyses were performed to assess the correlation between cell abundance and disease severity.

Macrophages and fibroblasts were identified as key communication hubs in UC; specifically, SPP1 + macrophages and CHI3L1 + fibroblasts were significantly enriched at the sites of inflammation. These cells are strongly correlated with disease severity and orchestrate inflammatory responses within the intestinal immune microenvironment, contributing to UC-associated colorectal cancer.

Our study identified SPP1 + macrophages and CHI3L1 + fibroblasts as key contributors to UC pathogenesis. These cells are enriched in inflammatory sites, are correlated with disease severity, and play a role in UC-associated colorectal cancer, providing new insights into UC mechanisms.

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.

Ayurvedic texts mention the use of Aegle marmelos fruit in colitis and other gastrointestinal ailments. The polyphenolic contents of the fruit, however, have poor bioavailability, limiting their therapeutic use. The study aimed to develop and optimise the A. marmelos fruit extract-phospholipid (AMEP) complex to improve the oral bioavailability of the A. marmelos extract (AME), and compare the in vivo effect of AME and AMEP in dextran sulfate sodium (DSS)-induced ulcerative colitis in rats.

The research work is the first of its kind to use a hydroalcoholic extract of A. marmelos fruit in the preparation of phospholipid complexes for ameliorating UC. The complexes were prepared using the solvent evaporation method and optimised by Box-Behnken design. The work compares the in vivo activity of plain AME, its phospholipid complexes, and the standard drug (mesalamine) in the alleviation of chemical-induced colitis in rats. AMEP was optimised using response surface methodology by Box-Behnken design. AMEP was characterised using scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, zeta analysis, and particle size analysis. A DSS-induced rat model was used in vivo studies to mimic ulcerative colitis. The pathogenesis of the disease was assessed by evaluating the levels of oxidative stress markers [nitric oxide (NO), malondialdehyde (MDA), and superoxide dismutase (SOD) activity], cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)], disease activity index, colon length, and histopathology.

The characterization confirmed the formation of AMEP, having a particle size of 673.6±4.30 nm, polydispersity index of 0.224±0.010, and zeta potential of -42.6 mV±0.51. The NO, MDA, TNF-α, and IL-6 levels were significantly reduced (p<0.0001, p<0.005, p<0.0001, p<0.01), and the SOD level was significantly increased (p<0.05) in AMEP-treated groups compared to the AME-treated groups.

These findings suggessts that AMEP has a powerful potential to reduce the levels of oxidative markers and inflammatory cytokines, making it a promising treatment for ulcerative colitis.

Ulcerative colitis (UC) is significantly linked with gut microbiota, which is essential for maintaining gut health. Their metabolites mitigate gut inflammation and bolster barrier function. Among these metabolites, we focused on vitamin B3, which has been reported to improve the pathogenesis of UC in mice. This study aimed to compare fecal vitamin B3 and gut microbiota between non-UC and UC patients.

We assessed fecal metabolites and gut microbiota in 71 UC patients (UC group) and 72 non-UC patients (non-UC group) matched by sex and age in 10-year intervals. Fecal samples were collected and metabolites were analyzed using capillary electrophoresis time-of-flight mass spectrometry. Bacterial DNA was extracted for 16S rRNA gene sequencing. We analyzed fecal nicotinamide levels and gut microbiota composition, employing statistical adjustments for confounding factors.

We found that the UC group exhibited significantly lower fecal nicotinamide levels and α-diversity (Shannon index) compared to the non-UC group. The relative abundance of bacterial genera such as Treponema, UCG-002, and Fusicatenibacter was decreased, while Sellimonas, Fournierella, and Oscillospira were increased in the UC group. Moreover, a negative correlation was observed between Sellimonas abundance and fecal nicotinamide levels in the UC group. Additionally, the UC group showed higher expression of a bacterial gene encoding nicotinamidase compared to the non-UC group.

These findings suggest that gut microbiota dysbiosis contributes to reduced vitamin B3 metabolism in UC patients. The study highlights the potential of replenishing vitamin B3 metabolic pathways as a novel therapeutic approach for UC treatment.

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.

Information on rates of safety outcomes in patients with ulcerative colitis [UC] is helpful to better understand the benefit-risk profile of more recent therapies approved for UC.

This narrative review provides an updated examination of the incidence and prevalence of safety outcomes in the UC patient population. Incidence and prevalence estimates were determined for outcomes including cardiac conduction disorders, infections, and malignancies from published literature [2013-2023].

While information for certain outcomes was more frequently recorded, such as herpes viral infection (incidence rate [IR] 0.0-4.47 per 100 person-years [PY]) and malignancies [all; IR 0.0-1.77 per 100 PY], rarer outcome estimates such as bradycardia [IR 0.2 per 100 PY] and macular edema [IR 0.2 per 100 PY] were limited. Our knowledge of certain, uncommon safety outcomes and concomitant medical conditions in the UC population remains limited given the lack of data available. Even though larger cohorts with longer follow-up are warranted, estimates provided in this review will contribute to an improved understanding of the safety profile of UC therapies.

To help navigate the complex treatment landscape of ulcerative colitis (UC), we quantified the benefit-risk trade-offs that patients were willing to make when choosing treatment.

Patients completed an online discrete choice experiment. Eligible patients had a UC diagnosis for ≥6 months, were aged ≥18 years, and resided in France, Germany, Italy, Spain, or the UK. Patients chose between 2 hypothetical treatments set up to ensure trade-offs were made. Clinical trial data, literature review, and patient interviews identified treatment attributes. Relative attribute importance (RAI) scores and maximum acceptable risks were generated. A patient-centric benefit-risk assessment of 200 mg of filgotinib was conducted as an example to show how measured trade-offs can be used.

Overall, 631 patients participated; patients had a mean age of 42.2 years and were predominantly male (75.3%). Achieving and maintaining clinical remission was the most important factor for patients (RAI 32.4%); to achieve this, patients were willing to accept slightly higher risks of blood clots, serious infections, and malignancies compared with lower risk treatment profiles. Patients also valued the convenience of oral treatments, avoiding steroids, and the ability to attend school/work. The patient-centric benefit-risk assessment suggested patients are significantly more likely to prefer Janus kinase 1 preferential inhibitor filgotinib over placebo.

Achieving clinical remission was the highest treatment priority for patients. To attain this, patients were willing to accept some slightly higher risk treatment profiles. Patient choices in the benefit-risk assessment suggested patients were significantly more likely to prefer filgotinib over placebo.

Administering beneficial bacteria as probiotics to restore the intestinal microbiota and its metabolic functions, such as butyrogenesis, is a promising treatment strategy in ulcerative colitis (UC). This study aimed to investigate the effect of a combination of probiotics, consisting of the lactic acid bacterium Weizmannia coagulans SANK70258 and the lactate-utilizing butyrate-producing bacteria Anaerostipes caccae or Clostridium butyricum, on the colonic environment using an in vitro colonic microbiota culture model with fecal inoculums from seven patients with UC. Co-inoculated W. coagulans and A. caccae neither inhibited each other's growth nor significantly affected the relative abundance of other bacterial species; however, the growth of W. coagulans was significantly inhibited when co-inoculated with C. butyricum. The relative abundance of pro-inflammatory bacteria (Escherichia sp. and unclassified Enterobacteriaceae) and Bifidobacterium spp. significantly decreased in W. coagulans-C. butyricum co-inoculated cultures. Inoculation with any of the probiotics alone did not increase butyrate production, whereas co-inoculation of W. coagulans with A. caccae or C. butyricum significantly increased the butyrate levels. Overall, the results suggested that W. coagulans and lactate-utilizing butyrate-producing bacteria in combination have synergistic effects through cross-feeding and can effectively restore butyrogenesis in the colonic environment of patients with UC. KEY POINTS: • Effects of probiotics were evaluated using in vitro microbiota model of UC colon. • W. coagulans and lactate-utilizing butyrate producers have synergistic effects. • Co-inoculation of W. coagulans with A. caccae or C. butyricum enhanced butyrogenesis.

The surgeries in drug-resistant ulcerative colitis are determined by complex factors. This study evaluated the predictive performance of radiomics analysis on the basis of whether patients with ulcerative colitis in hospital were in the surgical or medical treatment group by discharge from hospital.

This single-center retrospective cohort study used CT at admission of patients with US admitted from 2015 to 2022. The target of prediction was whether the patient would undergo surgery by the time of discharge. Radiomics features were extracted using the rectal wall at the level of the tailbone tip of the CT as the region of interest. CT data were randomly classified into a training cohort and a validation cohort, and LASSO regression was performed using the training cohort to create a formula for calculating the radiomics score.

A total of 147 patients were selected, and data from 184 CT scans were collected. Data from 157 CT scans matched the selection criteria and were included. Five features were used for the radiomics score. Univariate logistic regression analysis of clinical information detected a significant influence of severity (p < 0.001), number of drugs used until surgery (p < 0.001), Lichtiger score (p = 0.024), and hemoglobin (p = 0.010). Using a nomogram combining these items, we found that the discriminatory power in the surgery and medical treatment groups was AUC 0.822 (95% confidence interval (CI) 0.841-0.951) for the training cohort and AUC 0.868 (95% CI 0.729-1.000) for the validation cohort, indicating a good ability to discriminate the outcomes.

Radiomics analysis of CT images of patients with US at the time of admission, combined with clinical data, showed high predictive ability regarding a treatment strategy of surgery or medical treatment.

Inflammatory bowel diseases (IBD) are chronic conditions that can lead to a physical, social, and economic burden. Generative artificial intelligence (AI), particularly ChatGPT, gained attention for its potential to support medical practice. However, concerns remain about the reliability and consistency of its responses. This study systematically reviews the existing evidence on the role of generative AI in IBD.

We conducted a systematic literature review following PRISMA guidelines. Studies investigating generative AI in IBD care were identified through PubMed and Embase (Jan 2020-Sep 2024).

From 2875 records, 8 studies (2023-2024) met inclusion criteria: 5 on patient education, 2 on decision support, and 1 on research ideation. For patient education, ChatGPT provided clear and accurate responses, with accuracy reaching 84.2 % in a study, though sometimes lacked consistency. In decision support, ChatGPT's classifications of ulcerative colitis severity aligned with clinician assessments in 80 % of cases and in 87.8 % of cases for guideline-based dysplasia management. For research ideation, ChatGPT generated highly relevant (mean score: 4.9 ± 0.26) and clear (4.8 ± 0.41) questions, but lacked specificity (2.86/5) and originality (1.07/5).

Generative AI shows promise in IBD care, but concerns about accuracy, consistency, and outdated information highlight the need for expert oversight before clinical integration.

Data suggests 5-Aminosalicytes (5-ASA) medication does not influence outcomes in patients with moderate to severe ulcerative colitis (UC) on advanced therapy and can be discontinued. However, patients' perspectives on discontinuing UC-related medications have not been evaluated and should be incorporated when considering therapy changes. This study explored patients' experiences with UC treatment (5-ASA) in combination with advanced therapy, and barriers, facilitators, and attitudes toward deprescribing 5-ASAs.

To qualitatively evaluate patients' views on 5-ASA medication discontinuation two focus groups were conducted for patients with UC on stable doses of 5-ASA medication and advanced therapy for at least 6 months. Patients were asked about their satisfaction with and barriers to current therapy, quality of life, and opinions about the potential medication deprescribing. Transcripts were analyzed using an iterative inductive/deductive approach.

Ten patients participated with an average age 50 years (SD ± 11 years), 50% Female, and 80% White. Advanced therapy included tofacitinib (20%), vedolizumab (20%), or infliximab (20%). Qualitative analysis identified patient and clinician factors in the deprescribing process. Patient themes included emotions and coping, quality of life, attitudes and beliefs, experiences with the condition, and symptoms. Participants identify clinician themes including endorsement, communication, patient relationship, information distribution, and deprescribing readiness for change. The shared patient/clinician risk assessment was vital to moving towards deprescribing, however the decision to deprescribe was influenced by barriers and facilitators including further discussion with their clinician.

Patients with UC on advanced therapy and 5-ASA are open to deprescribing their 5-ASA but would have questions for their prescribing clinician including assurance of continued symptom management or ease of returning to the 5-ASA if needed.

Diet plays a crucial role in the activity and onset of ulcerative colitis (UC). The aim of this study was to comprehensively explore the association between the dietary inflammatory index (DII) and UC.

Participants completed the Food Frequency Questionnaire to obtain data on their dietary intake. Individual DII scores were calculated to assess inflammatory potential of each participant's diet. A logistic regression model was used to analyze the correlation between the DII and UC activity, including the active and remission phases.

In this study, 100 controls and 106 patients with UC were enrolled, including 50 patients in remission and 56 patients with active UC. Dietary nutrient intake was generally slightly lower in patients with UC than in the controls, including energy, protein, dietary fiber, vitamin D, vitamin E, vitamin B1, vitamin B2, vitamin C, folic acid, fat, monosaturated fatty acids, and n-3 fatty acids (P < 0.05). Compared with the low pro-inflammatory potential diet, patients with higher DII had a higher correlation with UC before and after adjustment for relevant confounders. In consecutive DII, the correlation with UC increased with each 1 increase in DII. No significant correlation was observed between DII and UC activity.

Diets with a high inflammatory index are correlated with UC. Therefore, consuming a diet with a low inflammatory index may be beneficial for patients with UC.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with a multifactorial etiology. Given the limitations and adverse effects of current therapies, there is a need for novel therapeutic approaches. Drug repurposing presents a promising opportunity to utilize medications with known safety and pharmacological profiles for alternative colitis treatment. Emerging evidence suggests the renin-angiotensin system (RAS) plays a significant role in the colitis pathophysiology. Angiotensin-converting enzyme (ACE) inhibitors may offer therapeutic potential by modulating pro-inflammatory cytokines and reducing oxidative stress. This study aims to evaluate the efficacy of lisinopril (LIS) in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model in Wistar rats. Colitis was induced in Wistar rats via a single intracolonic TNBS dose (100 mg/kg). Treatment groups received oral interventions for 5 days: 5-aminosalicylic acid (5-ASA; 25.5 mg/kg), LIS (10 mg/kg), or LIS (20 mg/kg). Efficacy was evaluated using the disease activity score rate (DASR), colon/body weight ratio (CBWR), and colon length, diameter, and pH. Colonic tissue was analyzed macroscopically and histopathologically. Inflammatory biomarkers interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), oxidative stress markers glutathione (GSH), and malondialdehyde (MDA), as well as C-reactive protein (CRP) and complete blood count (CBC), were measured. LIS significantly reduced colitis severity, decreasing DASR and CBWR, while restoring colon dimensions and pH. LIS showed potent anti-colitic effects by suppressing TNF-α and IL-6 levels, reducing MDA, and increasing GSH. LIS restored RBC and WBC levels while normalizing CRP and hemoglobin levels. Histopathological and macroscopic analyses confirmed colonic protection with minimal detrimental effects on the stomach and liver. LIS, particularly at 20 mg/kg, exhibited dose-dependent anti-inflammatory, antioxidant, and tissue-protective effects, showing promise as a therapeutic agent for colitis treatment.

Beetroot (Beta vulgaris L.) is well known for its medicinal uses, particularly in managing gastrointestinal disorders. This study investigates the protective effects of fresh red beet juice (FBRJ) on gastrointestinal complications caused by co-administration of dextran sulfate sodium (DSS) and loperamide (LOP), which induce ulcerative colitis and constipation, respectively.

Adult rats were divided into groups and subjected to a 7-day treatment with 5% DSS to induce ulcerative colitis, followed by LOP (3 mg/kg, body weight [b.w.]) for 7 days to cause constipation. FBRJ (5 and 10 mL/kg, b.w.) or yohimbine (YOH) (2 mg/kg, b.w.) was administered 1 h after LOP each day for 7 days. Therapeutic outcomes were evaluated based on macroscopic and histological changes in the gastrointestinal tract, gastric emptying, gastrointestinal transit, oxidative stress parameters, and inflammatory markers.

FBRJ significantly alleviated gastrointestinal dysfunctions caused by DSS and/or LOP, improving both gastric emptying and gastrointestinal transit in a dose-dependent manner (p < 0.05). Specifically, compared with the ulcerative/constipated group, the animals treated with the FBRJ showed a significant increase (52.43% ± 4.65% to 66.23% ± 6.78%) of gastric emptying (GE) andgastrointestinal transit (GIT: 48.08% ± 3.32% to 62.46% ± 4.98%) in a dose-dependent manner. It also modulated antioxidant defense systems by inducing enzyme activities and reducing lipid peroxidation, which had been significantly disrupted by the combined effects of DSS and LOP. Furthermore, inflammatory markers, including C-reactive protein (CRP), pro-inflammatory cytokines, and white blood cell counts, were significantly reduced in both plasma and colonic mucosa.

We suggest that FBRJ significantly protects against DSS-induced colitis and LOP-induced constipation, involving several mechanisms such as increasing secretion and peristaltic activity, reducing inflammation, and preserving the antioxidant properties.

Ulcerative colitis (UC) is characterized by abdominal pain and bloody diarrhoea and restoring the gut barrier is the core goal of UC treatment. Activation of aryl hydrocarbon receptor (Ahr) was reported to effectively alleviate symptoms and repair the gut barrier damage. Neutrophil extracellular traps (NETs) have been recognized as potential targets in the treatment of UC. Ahr activation has been found to be capable of upregulating Nqo1, thereby reducing the production of reactive oxygen species (ROS), which is important in the formation of NETs. Quercetin (QUE), which is derived from natural plants and herbs used in traditional Chinese medicine (TCM), is able to strengthen gut barrier function by activating Ahr.

The aim of this study is to investigate how QUE suppresses NETs in UC and activates Ahr in neutrophils.

In this study, the dextran sulfate sodium (DSS)-induced UC model was used. Histopathological assessments were performed in the paraffin slides of tissues after H&E, PAS, Masson and alcian blue staining. The concentration of cytokines was also detected using cytometric beads array kits. Based on the transcriptomic analysis of colon tissues, western blot (WB) analysis, immunohistochemistry (IHC) assays and immunofluorescence (IF) assays were conducted to validate the significantly regulated genes and pathways. In vitro, the binding of quercetin to Ahr was calculated by molecular dynamic simulations (MDS) and biolayer interferometry (BLI) analysis. Primary neutrophils isolated from mice were cocultured with LPS or PMA with or without quercetin. The regulated genes were detected using WB, real-time quantitative PCR, enzyme-linked immunosorbent assay (ELISA) and IF analysis. The agonists and antagonist of Ahr were used as the control.

After the administration of quercetin, colon inflammation and gut barrier disruption was significantly prevented through inhibiting the NF-κB pathway and upregulating the expression of Ahr/Arnt and Nqo1. The transcriptomic analysis and IHC assays showed that inflammation and NETs were greatly decreased by QUE treatment. In vitro, quercetin inhibited LPS-induced inflammatory responses through NF-κB pathway. Furthermore, MDS and BLI analysis revealed that QUE is an agonist of AHR. QUE activated Ahr translocation and reduced ROS production via regulation of Arnt and Nqo1.

This study proved that quercetin greatly improved gut barrier function in the DSS-induced colitis model by regulating NET formation and that quercetin was able to activate Ahr and upregulate Arnt in neutrophils to regulate NET formation.

Inflammatory bowel disease (IBD) is an immune-mediated, chronic, remitting, and relapsing disease. Calprotectin, used in monitoring the disease activity, is expressed from neutrophilic granulocytes during inflammation. Neutrophil gelatinase-associated lipocalin (NGAL) is strongly expressed in both granulocytes and the intestinal epithelial cell layer. The aim of the study was to compare fecal NGAL (FNGAL) with fecal calprotectin (FCAL) in children with IBD.

Forty-four children with IBD and 22 healthy children were included in the study. The patients were divided into two groups, patients with active disease and remission group. Clinical and demographic characteristics, disease activity scores, and serum and fecal markers of the patients were recorded.

The mean age of the patients was 13.2 ± 3.4 years (range 6-17 years) and male/female: 0.62. FNGAL levels of patients with active disease were higher than those in the remission group (p < 0.001). A statistically significant positive correlation was observed between Pediatric Ulcerative Colitis Activity Index scores and white blood cell count, platelets, neutrophil-to-albumin ratio (NAR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and FNGAL. There was a positive correlation between Pediatric Crohn's Disease Activity Index scores and platelets, NAR, ESR, CRP, and FNGAL, whereas there was a statistically significantly negative correlation with activity scores and albumin. While FNGAL had 95.5% sensitivity and 81.8% specificity, FCAL had 86.7% sensitivity and 85.7% specificity.

FNGAL levels were found to be high and sensitive in determining disease activity in our patients with IBD, suggesting that it may be a valuable biomarker.

Evidence for a potential link between dietary inflammatory potential and inflammatory bowel disease is limited, and the moderating role of genetic susceptibility remains to be assessed.

To evaluate energy-adjusted dietary inflammatory index (E-DII) for the associations with incident Crohn's disease (CD) and ulcerative colitis (UC) and the role of genetic susceptibility.

A total of 205,706 UK Biobank participants who were aged 39-72 years and had no known CD or UC at baseline (2006-2010) were included. The E-DII score was calculated based on energy-adjusted average intakes of 33 food or nutrient items derived from up to five 24-hour dietary recalls. Multivariable Cox regression models were used estimate hazard ratios (HRs) with 95% confidence interval (CI) for incident CD and UC.

During a median 12.3 years of follow-up, 382 incident CD and 798 incident UC cases were ascertained. A higher E-DII score was not associated with risk of CD (HR Q4 VS. Q1 = 1.28, 95% CI: 0.94-1.74; P-trend = 0.09) or UC (HR Q4 VS. Q1 = 1.10, 95% CI: 0.90-1.36; P-trend = 0.17). There was an interaction between the E-DII and the polygenic risk score (PRS) for CD on incident CD (P-interaction = 0.023), with an association only among participants with a high PRS (HR Q4 VS. Q1 = 1.64, 95% CI: 1.03-2.61) (P-interaction = 0.023). As compared with the participants with a low PRS for CD and a low E-DII score, participants with high levels of both scores had a particularly higher risk of CD (HR = 3.12; 95% CI: 1.74-5.60).

The association of dietary inflammatory potential with incident CD appears to be amplified by high genetic susceptibility to CD.