Maize bacterial stalk rot, caused by Erwinia carotovora pv. zeae (EC) is a significant threat to maize production, and applicable biocontrol measures are lacking. This study aims to identify a potent biocontrol agent against Erwinia carotovora and enhance plant growth under stress conditions. Thirty strains were screened using the agar plate well diffusion method. Strains PM57 and PM38 exhibited the highest antagonistic activity, forming inhibition zones of 5.0 and 4.51 mm, while distilled water served as a control with no inhibition. Their cell-free supernatants (CFSs) also demonstrated strong antagonistic activity with the maximum inhibition zones of 7.0 and 5.5 mm. The minimum inhibitory concentration of cell-free supernatants from both strains was 50 μg/ml. PM57 was identified as Bacillus subtilis via 16S rRNA gene sequencing. FTIR analysis revealed functional groups, including sulfonates, carbohydrates, proteins, and polyphenols in PM38, while PM57 exhibited peaks related to C-N stretching and aliphatic primary amine. GC-MS analysis identified twenty-six bioactive compounds known for their biological and medicinal properties, including tert-butyl phenol compounds, hydrocarbons, aldehydes, benzoquinones, pyrroles, and terpenes. Both inoculants produced volatile metabolites that effectively inhibited Erwinia carotovora growth in vitro. A greenhouse study revealed that PM57 reduced stalk rot disease incidence by 76.83 %, while PM38 reduced it by 74.94 %. The application of both inoculants enhanced chlorophyll activity; PM57 increased plant-growth by 11 %, and PM38 by 6 % and improved pathogen stress tolerance in maize seedlings compared to the positive control. These results demonstrate the potential of PM57 and PM38 as effective biocontrol agents for sustainable maize cultivation.

Inflammatory bowel disease (IBD) is a gastrointestinal inflammatory disorder characterized by disturbed interactions between gut microbiota and host immune response. Barley leaf (BL) is a traditional Chinese herb recorded to have health-promoting effects. However, little is known about the beneficial role of BL against enteric infection-induced intestinal inflammation. Here, we uncover that BL protects against Citrobacter rodentium (C. rodentium)-induced infectious colitis by improving host-microbiota interactions.

C3H/HeN mice were fed a diet with/without BL and infected with C. rodentium. Transcriptome sequencing, anti-CD4 antibody treatment, and flow cytometry were conducted to investigate the mechanisms of T cell immune modulation. The intervention involved administering anti-CD4 antibody at 500 µg each time for three times before and during C. rodentium infection. Analysis of gut microbiota composition was performed by 16S rRNA gene sequencing on fecal samples. Fecal microbiota transplantation was conducted by administering microbiota from donor group to recipient group via oral gavage to investigate the role of intestinal microbiota in immune modulation.

BL ameliorated the severity of C. rodentium-induced colitis, and this effect was linked to improved gut homeostasis and enhanced mucosal barrier function. BL enriched the pathways of T helper 1 (Th1)/Th2 and Th17 cell differentiation in the colon, suggesting the involvement of CD4+ T cells. Consistent with this, anti-CD4 antibody treatment abrogated the effect of BL and flow cytometry analysis revealed that BL mitigated C. rodentium-induced pro-inflammatory Th1 immune response. Moreover, the protective effect of BL was associated with alleviation of gut microbiota dysbiosis and increased abundance of Lactobacillus. Our in vivo studies further revealed that live Lactobacillus plantarum (L. plantarum) administration attenuated the pathogenic effects induced by C. rodentium infection, whereas heat-inactivated L. plantarum did not show the same results. Mechanistically, BL supplementation enriched L. plantarum, which subsequently released nanosized extracellular vesicles (EVs) that serve as a key mediator in alleviating C. rodentium-associated pathology and Th1 cell dysregulation.

Our work thus provides evidence for utilizing BL and L. plantarum-derived EVs to manage enteric infection-associated IBD.

Patients with inflammatory bowel disease (IBD) exhibit distinct shifts in circulating metabolite levels linked to disease activity and phenotype, but associations with disease progression remain unexplored. Our aim was to investigate relationships between circulating metabolites and metabolic pathways with disease progression risk in patients with IBD.

We performed an observational cohort study using the Mount Sinai Crohn's and Colitis Registry. Follow-up data were retrieved from longitudinal electronic health records. Untargeted metabolomic analysis was performed on baseline serum. Disease progression was defined as new systemic steroid or biological prescriptions, IBD-related hospitalization, or surgery. We used multivariable Cox proportional hazards (CoxPH) regression, L1-regularized CoxPH, and Random Survival Forest models to analyze metabolite associations with disease progression risk.

We studied 1292 metabolites in 277 patients with ulcerative colitis (UC) and 375 patients with Crohn's disease (CD). Over a median follow-up of 2 years, 57.5% experienced disease progression. In CD, 151 metabolites correlated with disease progression (false discovery rate [FDR] < 0.1): 81 (53.6%) associated with higher risk (enriched in amino acids, purine/pyrimidine metabolism, and bile acids) and 70 (46.4%) with lower risk (enriched in fatty acid oxidation, steroid biosynthesis, tryptophan, and antioxidants). In UC, 84 metabolites associated with disease progression (FDR < 0.1): 29 (34.5%) with increased risk (enriched in sphingolipids, hydrogen sulfide, and tyrosine metabolism) and 55 (65.5%) with decreased risk (enriched in steroid biosynthesis, histidine, and phenylalanine metabolism). Survival models incorporating a combination of metabolomic data and clinical parameters outperformed those based solely on clinical variables, including age, sex, disease location, disease behavior, disease extent, current and prior use of biologics, endoscopic disease activity, surgical history, and perianal disease.

Specific metabolites and pathways are associated with disease progression in IBD, highlighting potential prognostic biomarkers and relevant pathways.

Dual-layer spectral detector CT (DLCT) has several advantages in clinical practice, this study aims to reveal the clinical applications of DLCT in digestive system diseases.

We searched PubMed and Cochrane Reviews for articles published from January 1, 2010 to May 31, 2024, using the terms "dual-layer spectral detector CT" or "dual-layer CT" combined with "hepatic fat" or "hepatic fibrosis" "hepatocellular carcinoma" or "pancreatic ductal adenocarcinoma" or "pancreatic neuroendocrine tumors" or "gastric cancer" or "colorectal cancer" or "Crohn's disease" or "bowel ischemia" or "acute abdominal conditions".

DLCT consists of a top layer sensitive to lower-energy photons and a bottom layer sensitive to higher-energy photons. This configuration enables simultaneous acquisition of two energy spectra from a single X-ray beam ensuring consistent spatial alignment and temporal resolution. Spectral raw images allow image post-processing to improve image quality, reduce radiation doses and contrast media doses, and generate multiple quantitative parameters. It has broad potential for early detection, accurate staging, efficacy assessment, and prognosis prediction of liver, pancreatic, and gastrointestinal diseases, as well as for the assessment of digestive system vasculature.

DLCT not only provides valuable information for the clinical diagnosis and therapeutic effect evaluation of digestive system diseases but also may play a more important role in the overall management of digestive diseases and in the decision-making of individualized medicine.

Question What are the advantages of DLCT compared to traditional single-energy CT in the early detection, staging, and therapeutic evaluation of digestive system diseases? Findings DLCT enhances image quality, improves tissue characterization, and allows for multi-parametric analysis, making it superior in detecting and evaluating liver, pancreatic, and gastrointestinal diseases. Clinical relevance DLCT provides high-quality, multi-parametric imaging that improves the accuracy of diagnosing digestive diseases, facilitates more precise treatment planning, and enhances monitoring of treatment response, ultimately contributing to better patient management and prognosis.

Small bowel capsule endoscopy (SBCE) is a reliable method of evaluating small bowel mucosal lesions, and its use in Crohn's disease (CD) is increasing. We previously reported useful SBCE findings for early diagnosis of CD. In the present study, we developed a scoring model for early diagnosis of CD using SBCE findings.

We collected clinical and SBCE data of 110 patients with small bowel mucosal lesions and randomly divided them into derivation and validation cohorts. After selecting variables for scoring models by univariate analysis, the adopted model was determined. The score of each variable was based on the odds ratio obtained by multivariate analysis, and the cut-off value for the diagnosis of CD was examined by receiver operating characteristic analysis. Its reliability was verified in the validation cohort.

The model containing age (≤ 30 vs. ≥ 31), linear erosion, and circumferential alignment had the best fit (odds ratios of 4.97, 7.56, and 5.34, respectively). The linear erosion score was defined as 4 points, circumferential alignment as 4, and age of ≤ 30 years as 3. When the cut-off value was defined as 7 points, the scoring model had 85.4% sensitivity, 80.0% specificity, 83.7% positive predictive value, and 82.1% negative predictive value for diagnosis of CD. The validation cohort demonstrated an area under the curve of 0.93, similar to the derivation cohort.

We developed a scoring model for early diagnosis of CD based on SBCE findings, possibly contributing to the improvement of the long-term outcome of CD.

The Crohn's disease exclusion diet (CDED) has been shown to induce remission in adult Crohn's disease (CD) patients. The aim of the study is to provide additional evidence-based validation.

We conducted an open-label, randomized trial on adult CD patients with mild-to-moderate symptoms to assess CDED efficacy in inducing symptomatic remission using Mediterranean diet as control. We evaluate demographic data, body mass index (BMI), Harvey-Bradshaw Index (HBI), faecal calprotectin, and serum inflammatory indices at baseline, 12, and 24 weeks. Bioelectrical impedance analysis (BIA) was used to ensure the safety of the CDED group every 12 weeks.

Twenty-four patients were assigned to CDED, and 21 to controls, with no baseline differences among the parameters considered. Five CDED patients dropped out due to intolerance within the first 6 weeks. At 12 weeks, CDED patients showed significantly lower HBI and higher remission rates than controls. By 24 weeks, remission rates increased (70.8% vs. 38.1% at 12 weeks and 79.2% vs. 42.9% at 24 weeks; p = .027 and p < .0001, respectively), with significantly lower fibrinogen levels in the CDED group. The administration of CDED was associated with a significant decrease in BMI (25.8 kg/m2-24.5 kg/m2, p = .047), although BIA analysis showed a decrease in fat mass (18.2%-15.5%, p < .0001), while fat-free mass and body cellular mass significantly increased at 12 weeks (p = .001 and p = .042, respectively) and remained stable at 24 weeks.

The CDED was effective in inducing remission among patients with mild-to-moderate CD and appeared to be safe and well-accepted.

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.

Background: This study aimed to investigate the mechanisms by which PANoptosis of intestinal epithelial cells (IECs) promotes Crohn's disease (CD) progression. Methods: Single-cell RNA sequencing (scRNA-seq) was performed on inflamed and uninflamed colon tissues from patients with CD. The biological functions of intelectin-1 (ITLN1) in inflammation and PANoptosis were verified through in vitro experiments. The molecular mechanisms underlying its biological functions were examined using co-immunoprecipitation (Co-IP) combined with mass spectrometry (MS) and RNA-seq and further validated with rescue experiments. Additionally, the in vivo function of ITLN1 regulation on inflammation, PANoptosis, and the intestinal mucosal barrier was explored in interleukin-10 knockout (IL-10 KO) colitis model mice. Results: ITLN1 was significantly overexpressed in IECs from inflamed colon tissues and specifically associated with CD-related inflammatory markers. RNA-seq and in vitro experiments indicated that ITLN1 promotes inflammation, PANoptosis, and impaired tight junctions. Co-IP and MS analyses revealed that ITLN1 can bind to the PANoptosis-promoting protein calpain-2 (CAPN2) and enhance its stability. The E3 ubiquitin ligase, a tripartite motif containing 8 (TRIM8), directly interacts with CAPN2 and mediates its ubiquitination degradation. ITLN1 can bind to TRIM8, and its impact on inflammation and Z-DNA binding protein 1 (ZBP1)-induced PANoptosis can be antagonized by CAPN2. These in vivo studies indicated that short hairpin-ITLN1 improves colonic inflammation and intestinal barrier function in IL-10 KO mice. Conclusion: We identified the ITLN1-TRIM8-CAPN2 axis that drives IEC PANoptosis in CD progression. Pharmacological inhibition of ITLN1 significantly mitigated epithelial damage and colitis both in vivo and in vitro, establishing ITLN1-targeted therapies and PANoptosis modulation as viable clinical strategies for CD treatment.

Crohn's disease (CD) is a chronic, nonspecific inflammatory bowel disease with a poor prognosis. Despite its increasing incidence, curing CD remains challenging due to its complex etiology and unclear pathogenesis.

A comprehensive PubMed and Web of Science search was conducted using the keywords Crohn's disease, gut microbiota, dysbiosis, pathogenesis and treatment, focusing on studies published between 2014 and 2024.

Recent studies have demonstrated a close relationship between gut microbiota dysbiosis and the development of CD. Although many dysbioses associated with CD have not yet been proven to be causal or consequential, it has been observed that the gut microbiota in CD patients exhibits reduced diversity, a decrease in beneficial bacteria, and an increase in pathogenic bacteria. These changes may lead to decreased intestinal barrier function, abnormal immune responses, and enhanced inflammatory reactions, which are related to the disease's activity, phenotype, drug treatment efficacy, and postoperative therapeutic outcomes. Therefore, further exploration of the microbiota-host interactions and the pathogenesis of CD, the identification of biomarkers, and the development of targeted strategies for modulating the gut microbiota could offer new avenues for the prevention and treatment of CD.

This review highlights the pivotal role of gut microbiota dysbiosis in driving CD pathogenesis and its progression, while underscoring its potential as a therapeutic target through dietary modulation, microbial interventions, and integrative strategies to improve clinical management and prognostic outcomes.

A common complication which can influence the prognosis of Crohn's disease (CD) is multi-segmental strictures, and there are limitations to using either surgical or endoscopic treatment alone. We aimed to treat multi-segmental strictures in CD using combination of surgery and endoscopic therapy and to evaluate the efficacy and safety of conventional surgery combined with endoscopic stricturotomy for the treatment of deep small bowel multi-segmental fibrotic strictures.

21 patients with CD who underwent conventional surgery combined with endoscopic stricturotomy between January 2020 and December 2023 were included. Outcomes included immediate technical success, short- and long-term clinical efficacy, risk factors assessment, and analysis of adverse events. No risk factors were identified that would predict re-intervention.

The overall immediate success rate of the combined technique was 100%, with a 98.4% success rate for the endoscopic procedure alone. 85.7% of patients showed significant improvement in obstructive symptoms compared to the previous period, and only 9.5% required enteral nutrition, with the remainder resuming a regular diet by 8 weeks (all P < 0.0001). The median follow-up of the 21 patients was 528 days (IQR, 404-1296), with a one-year no re-intervention rate of 81.7% (95% CI, 70.6-90.2%). The incidence of adverse events of the procedure was 19%, 14% bleeding and 5% perforation, but all could be managed with intraoperative interventions without the need for postoperative re-intervention.

Surgery combined with endoscopic stricturotomy is a safe and effective treatment of multi-segmental fibrotic strictures in CD may provide a novel treatment option for strictures in CD.

Noncommunicable diseases (NCDs) associated with cardiovascular, neurological, and gastrointestinal disorders remain a leading cause of global mortality, sounding the alarm for the urgent need for better diagnostic and therapeutic solutions. Wearable and implantable biointegrated electronics offer a groundbreaking solution, combining real-time, high-resolution monitoring with innovative treatment capabilities tailored to specific organ functions. In this comprehensive review, we focus on the diseases affecting the brain, heart, gastrointestinal organs, bladder, and adrenal gland, along with their associated physiological parameters. Additionally, we provide an overview of the characteristics of these parameters and explore the potential of bioelectronic devices for in situ sensing and therapeutic applications and highlight the recent advancements in their deployment across specific organs. Finally, we analyze the current challenges and prospects of implementing closed-loop feedback control systems in integrated sensor-therapy applications. By emphasizing organ-specific applications and advocating for closed-loop systems, this review highlights the potential of future bioelectronics to address physiological needs and serves as a guide for researchers navigating the interdisciplinary fields of diagnostics, therapeutics, and personalized medicine.

Inflammatory bowel disease (IBD) refers to a chronic inflammatory condition involving the GI tract that includes Crohn's disease (CD) and ulcerative colitis (UC). These conditions are believed to arise in genetically predisposed individuals who develop an exaggerated immune response to the intestinal microbiota. A timely and accurate diagnosis of IBD is essential because diagnostic delays can result in intestinal damage that is irreversible, leading in some cases to intestinal dysfunction and the need for surgery. Diagnostic delays are common in cases when GI symptoms are mild and nonspecific. When IBD is suspected, the common diagnostic algorithm includes laboratory analyses, cross-sectional radiologic imaging, and endoscopy with biopsy and histological analysis. Other diagnostic biomarkers, including those found in the serum, stool, and urine, have also been evaluated in IBD. Newer artificial intelligence (AI)-based technologies are now being developed, and these will likely play an important future role in the diagnosis and management of IBD.

Crohn's disease is a chronic inflammatory disorder with rising global prevalence, marked by abdominal pain, diarrhea, and fatigue. Interleukin (IL)-23 plays a pivotal role in Crohn's disease pathogenesis, making it a therapeutic target. Risankizumab, a monoclonal antibody targeting the IL-23 p19 subunit, has shown potential in clinical trials.

This meta-analysis evaluates the efficacy and safety of Risankizumab in achieving clinical remission, clinical response, and endoscopic remission in patients with moderate-to-severe Crohn's disease.

A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines.

A comprehensive search of PubMed, Embase, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov was performed to identify randomized controlled trials (RCTs) assessing Risankizumab in Crohn's disease. Primary outcomes were clinical remission, clinical response, and endoscopic remission, with secondary outcomes focusing on treatment-related adverse events. A random-effects model estimated odds ratios (ORs) with 95% confidence intervals. Meta-regression analyzed dose- and duration-dependent effects.

Four RCTs involving 1774 participants showed that Risankizumab significantly improved clinical remission (OR = 2.223), clinical response (OR = 2.483), and endoscopic remission (OR = 4.112). Dose-dependent improvements were observed, with treatment duration affecting clinical remission (p = 0.0158) but not clinical response or endoscopic remission. Adverse event rates were comparable between Risankizumab and placebo groups (OR = 0.872, p = 0.592).

Risankizumab is effective in achieving clinical and endoscopic outcomes in moderate-to-severe Crohn's disease, demonstrating dose-dependent benefits and a favorable safety profile, supporting its use as a therapeutic option. However, the limited number of studies may affect the robustness of these findings. Further large-scale RCTs are needed to validate its long-term efficacy, safety in elderly populations, and effectiveness in biologic-naïve patients.

This systematic review and meta-analysis were registered with the INPLASY database under registration number INPLASY202530014. The full protocol is accessible at DOI: 10.37766/inplasy2025.3.0014.

Real-life data regarding inflammatory bowel disease (IBD) evolution after switch from intravenous infliximab (IV-IFX) to subcutaneous infliximab (SC-IFX) is necessary. The aim of this prospective multicenter cohort study was to describe the persistence, effectiveness and tolerance of SC-IFX after switch from IV-IFX.

IBD patients in steroid-free clinical remission for at least 6 months on IV-IFX were enrolled in a prospective national French cohort when they switched to SC-IFX. Patients were assessed at inclusion and at weeks 12, 24, and 48. The primary endpoint was the persistence of SC-IFX at week 48. Secondary endpoints comprised steroid-free clinical remission at week 48, IV-IFX switch-back rate, and evolution of infliximab levels during the study period.

Among the 426 patients included (72.4% with Crohn's disease , 27.5% with ulcerative colitis; 45.1% female; median age 37 [interquartile range, 29-50] years; median disease duration of 12 years in Crohn's disease, 13 years in ulcerative colitis), 56% were on IV-IFX standard dosing (5 mg/kg 8-weekly) and 16% received combination therapy with an immunomodulator drug at baseline. At week 48, SC-IFX persistence was 95.4% (95% confidence interval, 93.3%-97.5%) and 86.9% of patients were on steroid-free clinical remission. Mean infliximab levels were 8.0 μg/mL at inclusion and 18.0 μg/mL at week 48 (P < .0001). Among the 19 (4.5%) patients who stopped SC-IFX, 6 (1.4%) switched back to IV-IFX. There were 222 adverse events reported in 42.4% of patients, and 12 led to treatment discontinuation, including 6 (1.4%) severe adverse events.

In this large multicenter prospective cohort, persistence at 1 year of SC-IFX was more than 95% of IBD patients switched in remission from IV-IFX, confirming excellent effectiveness and tolerance of SC-IFX.

Intestinal inflammation and increased permeability have been linked to metabolic dysregulation in patients with compromised intestinal barrier function. Among the pathways, garnering attention is the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. Upon binding to double-stranded DNA (dsDNA), cGAS catalyzes the conversion of ATP and GTP into cyclic GMP-AMP (cGAMP). Subsequently, cGAMP binds to STING, triggering the activation of tank-binding kinase 1 (TBK1), which activates interferon regulatory factor 3 (IRF3), thus inducing the production of type I interferon. Activated TBK1 can also induce the activation of nuclear factor κB (NF-κB), thus mediating the production of proinflammatory cytokines. The effects of this process vary among innate and adaptive immune cells, as well as intestinal epithelial cells (IECs). This review aims to elucidate the impact and role of the cGAS-STING pathway on intestinal barrier function.

Polygonatum cyrtonema polysaccharides (PCP) exhibit ameliorative effects on colitis. However, whether the protective effects of PCP depend on the gut microbiota and how PCP regulates intestinal immune responses to alleviate colitis remain unclear. Therefore, this study investigated the effect of PCP against colitis focusing on the regulation of intestinal immune response. The PCP structure was reclassified as fructan. PCP treatment significantly reduced the symptoms of colitis. PCP restored IgA, ZO-1, Occludin, and MUC2 expression to enhance intestinal barrier function. Oral PCP administration markedly inhibited excessive inflammation-mediated immune response by modulating inflammatory cytokines secretion and Th17/Tregs cell balance and restored gut microbial composition. Interestingly, PCP still had a significant ameliorating effect on intestinal inflammation in colitis mice with gut microbial depletion by antibiotics. In the Caco-2/RAW264.7 co-culture inflammation model, PCP treatment improved the intestinal epithelial barrier function by regulating the inflammatory immune response through signal transduction pathways. Overall, these findings suggested that the alleviating effects of PCP on colitis are independent of gut microbiota, and that PCP can directly modulate the inflammatory immune response and intestinal barrier function, which in turn regulates gut microbiota. These findings will provide new insights into the action mechanism of natural polysaccharides in relieving colitis.

Cuproptosis represents a novel mechanism of cellular demise characterized by the intracellular buildup of copper ions. Unlike other cell death mechanisms, its distinct process has drawn considerable interest for its promising applications in managing inflammatory bowel disease (IBD) and colorectal cancer (CRC). Emerging evidence indicates that copper metabolism and cuproptosis may exert dual regulatory effects within pathological cellular environments, specifically modulating oxidative stress responses, metabolic reprogramming, and immunotherapeutic efficacy. An appropriate level of copper may promote disease progression and exert synergistic effects, but exceeding a certain threshold, copper can inhibit disease development by inducing cuproptosis in pathological cells. This makes abnormal copper levels a potential new therapeutic target for IBD and CRC. This review emphasizes the dual function of copper metabolism and cuproptosis in the progression of IBD and CRC, while also exploring the potential application of copper-based therapies in disease treatment. The analysis further delineates the modulatory influence of tumor immune microenvironment on cuproptosis dynamics, while establishing the therapeutic potential of cuproptosis-targeted strategies in circumventing resistance to both conventional chemotherapeutic agents and emerging immunotherapies. This provides new research directions for the development of future cuproptosis inducers. Finally, this article discusses the latest advances in potential molecular targets of cuproptosis and their related genes in the treatment of IBD and CRC, highlighting future research priorities and unresolved issues.

Crohn's disease (CD) is a chronic inflammatory bowel disease leading to symptoms such as abdominal pain, diarrhea, weight loss, fatigue, and complications such as strictures and fistulas. Ustekinumab (CNTO 1275) and briakinumab (ABT-874) are monoclonal antibodies that target the standard p40 subunit of the cytokines interleukin-12 and interleukin-23 (IL-12/23p40), which are involved in the pathogenesis of CD. Briakinumab has been withdrawn for the treatment of CD, making ustekinumab the only available antibody against the p40 subunit of interleukin-12 and interleukin-23 approved for this purpose.

To assess the benefits and harms of anti-IL-12/23p40 antibodies for induction of remission in CD, as compared to no treatment, placebo, other drug treatment, or varying dosing schedules.

We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and MEDLINE (from inception to 2 February 2024) and Embase (from inception until 12 August 2022). We also searched ClinicalTrials.gov, WHO ICTRP, references, and conference abstracts to identify additional studies.

We included randomized controlled trials (RCTs) of at least four weeks' duration in which monoclonal antibodies against IL-12/23p40 were compared to placebo, no treatment, or another active comparator in people with active CD. We also included trials examining different doses of antibodies against IL-12/23p40.

Two review authors independently screened studies for inclusion and extracted data. We assessed the methodological quality of the included studies using Cochrane's RoB 2 tool. The primary outcome was failure to induce clinical remission by week 8, or 6 to 12 as available. Secondary outcomes included failure to induce clinical improvement (clinical response), induction of endoscopic remission, quality of life, and adverse events, serious adverse events, and withdrawals due to adverse events. We calculated the risk ratio (RR) or risk difference (RD) and 95% confidence intervals (95% CI) for each outcome unless substantial heterogeneity was detected. We analyzed data on an intention-to-treat basis. We assessed the certainty of the evidence using the GRADE approach.

Eight RCTs involving a total of 3224 participants with CD met the inclusion criteria. All studies were double-blinded. We assessed the risk of bias for most outcomes as either low risk of bias or some concerns. Based on a pooled analysis of three trials, ustekinumab decreased the number of participants failing to achieve clinical remission at eight weeks when compared to placebo. Seventy-four per cent (693/938) of participants in the ustekinumab group and 87% (421/483) of those in the placebo group did not enter clinical remission (RR 0.85, 95% CI 0.81 to 0.89; 3 studies; 1421 participants; high-certainty evidence). Treatment with ustekinumab likely did not lead to more serious adverse events when compared to placebo, with 5% (48/966) and 6% (30/505) of participants affected in the ustekinumab and placebo groups, respectively (RD -0.01, 95% CI -0.03 to 0.01; 3 studies; 1471 participants; moderate-certainty evidence). A single small study in children compared two different induction doses of ustekinumab. The evidence for this outcome is very uncertain due to wide CIs. Eighty-one per cent (17/21) of participants receiving the higher induction dose (9 mg/kg or 390 mg) did not enter clinical remission at eight weeks, compared to 78% (18/23) of participants receiving the lower induction dose of 3 mg/kg or 130 mg (RR 1.03, 95% CI 0.77 to 1.39; 1 study; 44 participants; very low-certainty evidence). Separate safety data for the eight-week time point were not available for this comparison. Based on one trial comparing ustekinumab to adalimumab, the evidence is very uncertain about which is the more beneficial drug. Fifty per cent (95/191) of participants receiving ustekinumab did not enter remission compared to 52% (101/195) of participants receiving adalimumab (RR 0.96, 95% CI 0.79 to 1.17; 1 study; 386 participants; very low-certainty evidence). Separate results on adverse events at eight weeks were not reported for this comparison.

Ustekinumab reduces the risk of people with CD failing to enter clinical remission at eight weeks. It probably does not lead to more serious adverse events when compared to placebo. There were inadequate data to conclude the more effective induction dose of ustekinumab in children. No studies evaluated adverse events at eight weeks for this comparison. There may be little to no difference between ustekinumab and other biologics, such as adalimumab or guselkumab, in inducing clinical remission at week 8, but the evidence is very uncertain, and separate data on adverse events at eight weeks were not available.

This study investigated the safety and effectiveness of ustekinumab (UST) in Korean patients with Crohn's disease (CD).

Adult patients with CD treated with UST were prospectively enrolled in the K-STAR (Post-MarKeting Surveillance for Crohn's Disease patients treated with STelARa) study between April 2018 and April 2022. Both the clinical effectiveness and adverse effects of UST therapy were analyzed. Missing data were handled using nonresponder imputation (ClinicalTrials.gov Identifier: NCT03942120).

Of the 464 patients enrolled from 44 hospitals across Korea, 457 and 428 patients (Crohn's disease activity index ≥150) were included in the safety analysis and effectiveness analysis sets, respectively. At weeks 16 to 20 after initiating UST, clinical response, clinical remission, and corticosteroid-free remission rates were 75.0% (321 of 428), 64.0% (274 of 428), and 61.9% (265 of 428), respectively. At week 52 to 66, clinical response, clinical remission, and corticosteroid-free remission rates were 62.4% (267 of 428), 52.6% (225 of 428), and 50.0% (214 of 428), respectively. Combined effectiveness (clinical response + biochemical response) was achieved in 40.0% (171 of 428) and 41.6% (178 of 428) at week 16 to 20 and week 52 to 66, respectively. Biologic-naïve patients exhibited significantly higher rates of combined effectiveness than biologic-experienced patients (50.3% vs 30.7% at week 16-20, P < .001; 47.7% vs 36.0% at week 52-66, P = .014). No additional benefits were observed with the concomitant use of immunomodulators. Ileal location was independently associated with a higher probability of clinical remission compared with colonic or ileocolonic location at week 52 to 66. Adverse and serious adverse events were observed in 28.2% (129 of 457) and 12.7% (58 of 457), respectively, with no new safety signal associated with UST treatment.

Ustekinumab was well-tolerated, effective, and safe as induction and maintenance therapy for CD in Korea.

The care needs of patients with Crohn's disease (CD) may be heterogeneous. This study aimed to explore the latent class of care needs of patients with CD and differences in their characteristics and to analyze the factors influencing the different latent classes.

A convenience sampling method was used to select 250 patients with CD who attended a tertiary-level hospital in Nanjing from August to November 2024 for the study. They were surveyed via the General Information Questionnaire, the Crohn's Disease Care Needs Scale (CD-CNS), the Inflammatory Bowel Disease (IBD) Patient Symptom Clusters Assessment Scale, the Family Adaptability and Cohesion Scale (FACES), and the Post-traumatic Growth Inventory (PTGI). The latent classes of care needs of CD patients were identified via latent profile analysis (LPA), and the factors influencing their latent classes were analyzed via multiple logistic regression analyses.

(1) The LPA results revealed that the care needs of CD patients were divided into three profiles as the best model fitting indicators: the "low-care-needs-adaptation group" (n = 96, 38.4%), the "moderate-care-needs-growth group" (n = 81, 32.4%), and the "high-care-needs-distress group" (n = 73, 29.2%). (2) Regression analyses revealed that current disease status, the presence of a stoma, symptom burden, family adaptability and cohesion, and post-traumatic growth (PTG) were influential factors in different latent classes.

There is significant heterogeneity in the care needs of CD patients. Care needs to focus on patients with high care needs and enhance their symptom management and psychological interventions to improve their PTG and reduce their disease burden.

To investigate the feasibility of using 18F-fibroblast activation protein (FAP) inhibitor positron emission tomography/computed tomography (18F-FAPI PET/CT) to detect intestinal fibrosis in its early stages and identify its severity in a mouse model.

A dextran sulfate sodium (DSS)-induced mouse model of intestinal fibrosis was established. To detect pro-inflammatory cytokines and histopathology, blood and intestinal lesion samples were collected after 18F-FAPI PET/CT scanning (3.7 MBq/mice) at 3, 6, 9, and 12 weeks post-initial exposure to DSS. Correlation and diagnostic efficacy were explored between 18F-FAPI uptake and FAP expression or fibrosis score in early, late, and entire stages of intestinal fibrosis.

18F-FAPI uptake was positively correlated with FAP expression throughout entire stages of intestinal fibrosis (r = 0.90). However, a weak correlation between 18F-FAPI uptake and fibrosis score (r = 0.49), and moderate diagnostic performance of 18F-FAPI PET for fibrotic severity (area under the receiver-operating characteristic curve [AUC] = 0.79) were found throughout the entire stages. Interestingly, in the early stages, 18F-FAPI PET effectively distinguished the degree of intestinal fibrosis (AUC = 0.95), and was strongly correlated with fibrosis score (r = 0.89). In the late stages, the diagnostic efficacy (AUC = 0.46) and correlation (r = -0.20) drastically decreased.

As Crohn's disease (CD) with intestinal fibrosis progresses, 18F-FAPI uptake is high in the early stages and then gradually decreases. Activated fibroblasts appear more frequently in the early stages of intestinal fibrosis indicates that 18F-FAPI PET has a great potential for early identification of intestinal fibrosis and provides new insights into treatment decision-making in CD patients.

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.

Psoriasis and Crohn's disease (CD) are chronic inflammatory diseases that involve complex immune-mediated mechanisms. Despite clinical overlap and shared genetic predispositions, the molecular pathways connecting these diseases remain incompletely understood. The present study seeks to identify shared biomarkers and therapeutic targets for psoriasis and CD.

Differentially expressed genes (DEGs) were identified from publicly available transcriptomic datasets related to psoriasis and CD. Simultaneously, weighted gene co-expression network analysis (WGCNA) was performed to identify gene modules associated with the clinical traits of psoriasis and CD. Subsequently, biomarkers were prioritized from shared key genes by integrating protein-protein interaction (PPI) networks with machine learning models. Gene Set Enrichment Analysis (GSEA), along with Gene Ontology (GO) and KEGG pathway analyses, were performed to determine the biological significance of the identified genes. Immune infiltration analysis underscored the involvement of hub genes in immune regulation, while single-cell transcriptomic analysis revealed the cellular localization of these hub genes. Additional targeted molecular biology experiments validated the shared biomarkers. DSigDB predictions were employed to identify potential therapeutic compounds. Molecular docking simulations were performed to assess the binding affinity of the drugs to key target proteins. Finally, additional in vitro experiments were conducted to validate the therapeutic effects of the identified compounds.

The study identified KIF4A, DLGAP5, NCAPG, CCNB1, and CEP55 as key regulatory molecules and shared biomarkers for both diseases. GSEA and pathway analysis highlighted the importance of cell cycle regulation and immune response pathways in the comorbidities of psoriasis and CD. Immune infiltration analysis emphasized the role of hub genes in immune regulation. Furthermore, DSigDB predictions and molecular docking simulations indicated strong therapeutic potential for Etoposide, Lucanthone, and Piroxicam, with Etoposide showing the highest affinity for key targets. In cellular models, Etoposide demonstrated promising therapeutic effects by significantly downregulating the expression of psoriasis-related keratinocytes marker genes (KRT6, KRT16) and CD-related inflammatory cytokines (IL6, IL8, TNF-α), highlighting its potential in treating psoriasis and CD.

This study integrates bioinformatics, machine learning, and molecular validation to identify the shared molecular mechanisms of psoriasis and CD, uncovering novel biomarkers and potential combined therapeutic candidates. These findings provide valuable insights into potential treatment strategies for these diseases.

Crohn's Disease (CD), an inflammatory bowel disorder, is influenced by genetic, immune, and environmental factors. The present study highlights the pioneering role of circular RNAs (circRNAs) in the etiology of CD, with a specific focus on hsa_circ_0005255 and its regulatory role. Utilizing both bioinformatic and experimental approaches, we exposed the mechanistic and therapeutic significance of hsa_circ_0005255 within the pathophysiological framework of CD. Our findings revealed a significant underexpression of hsa_circ_0005255 in tissue samples from CD patients and in DSS-induced CD mouse models. The overexpression of hsa_circ_0005255 markedly mitigated inflammatory responses, as indicated by decreased serum levels of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6, and reduced histopathological indications of inflammation in colonic tissues. It substantially improved the integrity of the epithelial barrier, evidenced by the upregulation of Zonula Occludens-1 expression and the reduction of apoptosis in colonic epithelial cells. Furthermore, this regulatory effect extended to the enhancement of epithelial cell proliferation and autophagy, characterized by the elevated expression of Ki-67, microtubule-associated protein 1A/1B-light chain 3 II, and Beclin-1, along with the suppression of cleaved caspase-3 and sequestosome 1. Mechanistically, hsa_circ_0005255 functioned as a competitive endogenous RNA, absorbing miR-23a-3p and thereby regulating Nuclear Receptor Coactivator 3. This investigation not only broadens our understanding of the involvement of circRNAs in CD pathogenesis but also identifies hsa_circ_0005255 as a potent biomarker and therapeutic target.

Autophagy is a pro-survival process that regulates the degradation and renewal of cellular components, making it a crucial mechanism for cellular homeostasis. There are selective forms of autophagy that are specific to a number of substrates, such as pathogens (bacteria or viruses), protein aggregates or excess/damaged organelles. These processes involve as key players autophagy receptors, that link the cargo to be degraded to the autophagic machinery. Among them, NDP52 (also known as CALCOCO2) has been described to act as a "bridge" between the autophagy machinery and (1) damaged mitochondria in the mitophagy process; (2) pathogens during xenophagy or (3) proteins in the process of aggrephagy. The aim of this review is to summarize the major functions of NDP52, and to highlight the existence of two human NDP52 variants that have been described as risk or protective factors for Crohn's disease or Multiple Sclerosis and Alzheimer's disease patients, respectively. As these three diseases share common pathological features that lead to inflammation, such as mitochondria or gut microbiota dysfunctions, but also pathogenic infections, it seems clear that NDP52 could be a key player at the crossroad by acting indirectly on inflammation, and therefore a potential target for clinical applications and benefits.

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.

Iron and copper are essential metal ions, and maintaining their metabolic balance is critical for organismal health. The Six-Transmembrane Epithelial Antigen of the Prostate (STEAP) protein family, comprising STEAP1, STEAP2, STEAP3, and STEAP4, plays a vital role in cellular metal homeostasis. These proteins are located on the cell membrane and are characterized by six transmembrane domains. With the exception of STEAP1, the STEAP proteins function as metal oxidoreductases due to their F420H2:NADP+ oxidoreductase (FNO)-like domain. However, STEAP1 contributes to metal metabolism through its heme group and interaction with other STEAP proteins. Beyond metal metabolism, STEAP proteins are involved in critical cellular processes, including the regulation of the cell cycle, proliferation, differentiation, and apoptosis. Notably, STEAP proteins are recognized as potential biomarkers and therapeutic targets in human cancers, particularly prostate cancer. This review outlines the structural features and functional roles of STEAP proteins in various diseases, including cancers, insulin resistance, non-alcoholic fatty liver disease (NAFLD), and benign prostatic hyperplasia, with a focus on their potential for therapeutic intervention.

This study aimed to investigate the effects of environmental benzene exposure and its interaction with genetic susceptibility on inflammatory bowel disease (IBD), with a specific focus on ulcerative colitis (UC) and Crohn's disease (CD).

A total of 432,727 participants from the UK Biobank who were free of IBD at baseline were included in the analysis. The annual average benzene concentrations during the follow-up period were evaluated by air dispersion models. The study assessed the incidence of IBD in relation to ambient benzene exposure using Cox proportional hazard models and estimated the exposureresponse relationships using restricted cubic spline models. Additive interactions included relative excess risk due to interaction (RERI) and the attributable proportion (AP) to evaluate the interaction between ambient benzene exposure and genetic predisposition.

A significant association was identified between ambient benzene exposure and the incidence of IBD, with hazard ratios (95 % confidence intervals) of 1.06 (1.03, 1.09) for IBD, 1.08 (1.04, 1.12) for UC, and 1.03 (0.98, 1.09) for CD per 0.1 μg/m3 increase. Furthermore, genetic predispositions were found to significantly modify the relationship between ambient benzene exposure and IBD risk. Individuals with the highest genetic risk and benzene exposure had the highest risk of UC.

This study provides compelling evidence of the interaction between environmental factors and genetic susceptibility in the pathogenesis of UC. These findings underscore the importance of considering both genetic and environmental influences in future prevention and intervention strategies for IBD.

To conduct a meta-analysis of the factors influencing sarcopenia in patients with Crohn's disease and provide evidence-based findings for early clinical detection and prevention.

The study was registered on PROSPERO(CRD42023470300). A systematic review was performed on literature pertaining to sarcopenia in patients with Crohn's disease utilizing eight Chinese and English databases, which consist of CNKI, Wanfang, VIP, CBM, PubMed, Web of Science, Embase, and The Cochrane Library. The search was carried out from the inception of each database until October 8, 2023. Data analysis was carried out using the Stata 14.0 software.

A total of 603 Chinese and English literature sources were reviewed, and following the application of the inclusion and exclusion criteria, 9 articles were selected. These 9 articles take into account a total of 22 factors that may influence the occurrence of sarcopenia in Crohn's disease patients. The results of the meta-analysis demonstrate that gender (OR=5.49, 95 % CI [2.08,14.51]), BMI (OR=0.77, 95 % CI [0.62,0.95]), age (OR=1.03, 95 % CI [1.01,1.05]), and low albumin levels (OR=1.08, 95 % CI [1.01,1.15]) have significant impacts on the emergence of sarcopenia in patients with Crohn's disease.

The occurrence of sarcopenia in Crohn's disease patients is mainly influenced by gender, BMI, age, and low albumin levels. Additional factors that may influence the condition require further research to verify.

The long-term efficacy and safety of infliximab (IFX) in Japanese children with inflammatory bowel disease (IBD) remain unclear. This study aimed to examine the long-term outcomes of IFX treatment in Japanese children with IBD.

We retrospectively recruited patients aged <16 years who were diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) at Kurume University Hospital in Japan between 2011 and 2022 and examined the effectiveness and safety of IFX. We characterized the responses to IFX as primary response, primary nonresponse (PNR), secondary loss of response (sLOR), or still receiving IFX.

Among the 77 enrolled patients with UC (median age, 10 years) and 48 with CD (median age, 12 years), 55 (27 with UC and 28 with CD) received IFX treatment. IFX treatment was significantly more common in patients with CD (58.3%) than in those with UC (35.1%; p=0.016). The PNR was significantly greater in patients with UC (18.5%) than in those with CD (0.0%; p=0.023), as was the sLOR (UC, 51.9%; CD, 21.4%; p=0.026). The likelihood of continuing IFX treatment during follow-up (median, 38 months) was significantly higher in patients with CD (71.4%) than in those with UC (29.6%; p=0.003). Adverse events resulting in the discontinuation of IFX occurred in 3.6% of the patients; one patient with CD developed leukemia, and the other had a serious infusion reaction.

The long-term durability of IFX in Japanese pediatric patients with IBD was inadequate in UC compared with CD. Serious adverse events in 3.6% of patients required discontinuation.

Wearable devices capture physiological signals noninvasively and passively. Many of these parameters have been linked to inflammatory bowel disease (IBD) activity. We evaluated the associative ability of several physiological metrics with IBD flares and how they change before the development of flare.

Participants throughout the United States answered daily disease activity surveys and wore an Apple Watch (Apple), Fitbit (Google), or Oura Ring (Oura Health). These devices collected longitudinal heart rate (HR), resting heart rate (RHR), heart rate variability (HRV), steps, and oxygenation. C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin were collected as standard of care. Linear mixed-effect models were implemented to analyze HR, RHR, steps, and oxygenation, and cosinor mixed-effect models were applied to HRV circadian features. Mixed-effect logistic regression was used to determine the predictive ability of physiological metrics.

Three hundred and nine participants were enrolled across 36 states. Circadian patterns of HRV differed significantly between periods of inflammatory flare and remission and symptomatic flare and remission. Marginal means for HR and RHR were higher during periods of inflammatory flare and symptomatic flare. There were fewer daily steps during inflammatory flares. HRV, HR, and RHR differentiated whether participants with symptoms had inflammation. HRV, HR, RHR, steps, and oxygenation were significantly altered up to 7 weeks before inflammatory and symptomatic flares.

Longitudinally collected physiological metrics from wearable devices can identify and change before IBD flares, suggesting their feasibility to monitor and predict IBD activity.

Advances in understanding the pathogenesis of inflammatory bowel disease (IBD) point toward a key role of the gut microbiome. We review the data describing the changes in the gut microbiome from IBD case-control studies and compare these findings with emerging data from studies of the preclinical phase of IBD. What is apparent is that assessing changes in the composition and function of the gut microbiome during the preclinical phase helps address confounding factors, such as disease activity and drug therapy, which can directly influence the gut microbiome. Understanding these changes in the predisease phase provides a means of predicting IBD in high-risk populations and offers insights into possible mechanisms involved in disease pathogenesis. Finally, we discuss strategies to use this information to design interventions aimed at modulating the microbiome as a means of preventing or delaying the onset of IBD.

Efferocytosis, the process by which apoptotic cells (ACs) are recognized and cleared by phagocytes, is a critical mechanism in maintaining intestinal immune homeostasis and promoting the resolution of inflammation. Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic intestinal inflammation, wherein defective efferocytosis contributes to the accumulation of ACs, secondary necrosis, and sustained mucosal damage. This review delineates the molecular mechanisms underlying efferocytosis and systematically examines its functional roles across five key intestinal phagocytic cell types: macrophages, dendritic cells (DCs), neutrophils, intestinal epithelial cells (IECs), and Paneth cells (PCs). Particular emphasis is placed on the dysregulation of efferocytosis capacity in IBD pathogenesis and the consequences of impaired apoptotic cell clearance in both professional and non-professional phagocytes. Furthermore, we evaluate emerging therapeutic strategies designed to restore or enhance efferocytosis, including modulation of macrophage polarization, LC3-associated phagocytosis pathways, nanotechnology-enabled delivery systems, and stem cell-based interventions. A comprehensive understanding of cell-type-specific efferocytosis in the intestinal microenvironment offers promising directions for the development of targeted, inflammation-resolving therapies for IBD.

Upadacitinib is a selective Janus kinase-1 inhibitor, approved for the management of Crohn's disease (CD) by the United States Food & Drug Administration. In Greece, upadacitinib was initially available through an early-access program. Our goal was to describe the real practice experience.

This was a multicenter retrospective cohort study of patients with moderate-to-severe CD. The primary endpoint was clinical response, defined as a reduction ≥3 in the Harvey-Bradshaw index. Secondary endpoints included biochemical improvement. Outcomes were assessed at 4, 8 and 12 weeks.

A total of 24 CD patients received upadacitinib and were included in the analysis. Their mean age was 42.2 years (range 24-63). Eleven patients (45.8%) had ileocolonic CD and 5 (20.8%) CD colitis. Fourteen patients had active extraintestinal manifestations. The majority of patients (19/24) had ≥3 failed biologics. All of them had failed treatment with anti-tumor necrosis factor and 19 (79%) with ustekinumab. At 12 weeks, nearly all patients achieved a clinical response (85%). Of 13 patients with C-reactive protein >5 mg/L at baseline, 11 (84.6%) achieved normalization by week 8. Adverse events occurred in 3 patients (14.2%).

In a small cohort of resistant CD patients, the short-term clinical efficacy of upadacitinib was high.

Background/Objectives: The histological involvement of surgical resection margins in Crohn's disease (CD) is an important risk factor for postoperative recurrence. The aim of this study was to evaluate the usefulness of intraoperative ultrasonography (IOUS) of the small bowel to best identify the surgical site of resection and reduce the rate of the histological involvement of margins. Methods: Consecutive patients who underwent ileocolic surgery for CD were prospectively enrolled (IOUS group) and underwent IOUS to fix the resection site. A control historical group of patients undergoing the same surgical procedures was considered and a 1:1 propensity score matching for location of disease and repeated surgery was performed. The primary endpoint was the histological involvement of resection margins. The secondary endpoint was to assess the feasibility of the method. Results: Twenty-seven patients were enrolled in the IOUS group and twenty-seven were enrolled in the non-IOUS group. The two groups were homogeneous in terms of gender, age, smoking, BMI, behavior of disease, and surgical technique. The IOUS group presented a lower rate of histological positive margins (18.5% vs. 48.1%; p = 0.021). No significant differences were found in terms of mean duration of surgery (IOUS: 254.2 min vs. non-IOUS: 225 min [SD = 49.3-77.8]; p = 0.11) or in terms of mean length of surgical specimen (IOUS: 24.1 cm vs. non-IOUS: 34.1 cm [SD = 13.5-23.1]; p = 0.058). Conclusions: IOUS of the small bowel appears to be a useful tool to obtain a lower rate of histologically positive margins with a comparable duration of surgery and no significant difference in the intestinal specimen length.