Search

Background: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Ginsenoside may be an ideal agent for UC treatment. However, its efficacy and safety are unknown. We aim to conduct a systematic evaluation to assess the effects and potential mechanisms of ginsenosides in animal models of UC. Methods: Six electronic databases will be searched (PubMed, Embase, Web of Science, China Knowledge Network (CNKI), China Science and Technology Journal Database (CQVIP), and Wanfang Data Knowledge). SYRCLE list will be used to assess the quality of literature, and STATA 15.1 for data analysis. Time-dose effects analysis will be used to reveal the time-dosage response relations between ginsenosides and UC. Results: Ultimately, fifteen studies involving 300 animals were included. Preliminary evidence was shown that ginsenosides could reduce Disease Activity Index (DAI) scores, weight loss, histological colitis score (HCS), spleen weight, Malondialdehyde (MDA), Myeloperoxidase (MPO) activity, interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and increase colon length (CL), myeloperoxidase (GSH), interleukin 4 (IL-4), interleukin 10 (IL-10), Zonula Occludens-1 (ZO-1) and occludin. Results of time-dose interval analysis indicated that ginsenosides at a dosage of 5–200 mg/kg with an intervention time of 7–28 days were relatively effective. Conclusions: Preclinical evidence suggests that ginsenoside is a novel treatment for UC. And the mechanisms of ginsenosides in treating UC may involve anti-inflammatory, antioxidant, barrier protection, intestinal flora regulation, and immune regulation. Although, due to the high heterogeneity, further large-scale and high-quality preclinical studies are needed to examine the protection of ginsenosides against UC. [ABSTRACT FROM AUTHOR]

Introduction: Inflammatory bowel disease (IBD), consists of two primary types: Ulcerative Colitis (UC) and Crohn's Disease (CD). Infliximab (IFX) and Adalimumab (ADA) are frequently utilized in the management of moderate to severe cases of IBD. Aim: This study aimed to assess the efficacy and safety of IFX and ADA in individuals diagnosed with moderate to severe IBD. Method: This study is a prospective open-labeled randomized parallel study that included moderate to severe IBD patients treated with either IFX or ADA. A total of 56 patients participated, with 34 patients received IFX and 22 patients received ADA. Various measures, including Crohn's Disease Activity Index (CDAI), Mayo Score/ Disease Activity Index (DAI), and C-reactive protein (CRP) levels, were taken at baseline and week 14 to assess the efficacy of the treatments. In addition, the levels of drugs and sTREM-1 were measured at 14 weeks. Patient safety was monitored throughout the study period. Results: In the group received IFX, there was a notable decrease in CDAI (P = 0.045), DAI (P = 0.026), and CRP (P = 0.023 for CD, and P = 0.021 for UC) levels. In addition, the group received ADA experienced a significant reduction in CDAI (P = 0.001), DAI (P = 0.032), and CRP (P < 0.018 for CD and P = 0.003 for UC) levels. Responders had higher drug concentrations than non-responders, notably IFX concentration was higher in responders with CD (P = 0.001) and UC (P < 0.001). ADA concentration was higher in UC (P <= 0.001) and all CD patients responded to the treatment. The same trend was observed for sTREM-1 levels in CD and UC patients (P = 0.042, and P = 0.015, respectively) in the IFX group. In UC patients treated with ADA, the level of sTREM-1 was significantly low (P = 0.002). Conclusion: Both IFX and ADA have a good safety profile and deliver a beneficial clinical and laboratory response in moderate-severe IBD patients. Clinical Trial Registration: This study is registered on ClinicalTrials.gov under the identifier NCT05291039. (You can access the study at https://clinicaltrials.gov/study/NCT05291039 (First Posted: March 22, 2022). [ABSTRACT FROM AUTHOR]

Background: Early detection of ulcerative colitis-associated neoplasia (UC-N) remains a clinical challenge. Identification of molecular biomarkers for colorectal dysplasia and cancer may be extremely beneficial in early detection and managing cancer risk in longstanding ulcerative colitis (UC) patients. Objective: The aim of this work is to investigate the role of Reg IV in comparison to P53 and KRAS in UC-associated dysplasia and colorectal cancer (CRC) in order to evaluate the potential use of Reg IV for dysplasia and cancer screening in UC patients. Methods: The study was conducted on 5 groups each 20 colonic endoscopic samples: 1) Normal colonic mucosa, 2) Active UC without dysplasia/carcinoma, 3) UC-associated dysplasia, 4) UC-associated CRC (UC-CRC), 5) Sporadic CRC. All included cases were subjected to Reg IV mRNA expression analysis by quantitative reverse transcription polymerase chain reaction, and immunostaining for Reg IV, P53 and KRAS. Results: Reg IV mRNA expression levels were found to be significantly higher in groups 3 and 4 (mean: 3.37 and 5.70, respectively). Reg IV immunostaining was highly expressed in groups 3 and 4 (mean: 45.80 and 62.35, respectively). While P53 and KRAS immunostaining was highly expressed in group 5 (mean: 64.57 and 62.90). Furthermore, Reg IV immunoexpression had shown a negative correlation with P53 and KRAS immunoexpression in groups 4 and 5. Conclusion: Higher expression of Reg IV in patients with UC-dysplasia and UC-CRC versus KRAS and P53 expression in sporadic CRC, suggests a potential role of Reg IV in UC carcinogenesis pathway. This could advocate the use of Reg IV as a screening biomarker for UC-N among patients with long-standing UC as well as a promising targeted therapeutic strategy. [ABSTRACT FROM AUTHOR]

Objective(s): Ulcerative colitis (UC) is a commonly recurrent inflammatory bowel disease. T helper 17 (Th17)/regulatory T (Treg) cell balance plays an essential role in UC progression. However, it is unknown whether curcumin chitosan microspheres (CCM) regulate the Th17/Treg cell balance. Materials and Methods: The UC mouse model was established by administering 3% dextran sodium sulfate and treated with CCM. The influence of CCM on the Th17/Treg balance was detected using flow cytometry. Cell experiments were conducted to investigate the role and mechanism of IGF2BP1 in Th17/Treg balance. Results: We revealed that CCM demonstrated a significant therapeutic effect on UC. CCM obviously decreased the Th17 cell percentage but boosted the Treg cell percentage in UC mice. CCM remarkably increased the mRNA expression of Foxp3 but suppressed RORγt and interleukin-10 mRNA expression. PCR array of RNA modification-related genes revealed that the m6A binding protein IGF2BP1 was a key molecule in CCM regulation of Th17/Treg balance. IGF2BP1 overexpression dramatically repressed the CCM-induced balance of Th17/Treg cell differentiation. Mechanically, IGF2BP1 targeted LRP5 and regulated LRP5 through m6A modification. Furthermore, the silencing of LRP5 canceled the suppressive effect of IGF2BP1 on Th17/Treg cell percentage. Conclusion: CCM modulated the Th17/Treg balance through IGF2BP1-mediated m6A modification, thereby alleviating UC, and providing new ideas for the treatment of UC. [ABSTRACT FROM AUTHOR]

[Display omitted] Berberine (Ber), an isoquinoline alkaloid, is a potential drug therapy for ulcerative colitis (UC) because of its anti-inflammatory activity, high biological safety, and few side effects. Nevertheless, its clinical application is hindered by its limited water solubility and low bioavailability. Currently, compared to synthetic nanocarriers, exosomes as carriers possess advantages such as low toxicity, high stability, and high specificity. Human placental mesenchymal stem cell-derived exosomes (HplMSC-Exos) have emerged as a promising drug delivery system, offering intrinsic anti-inflammatory and antioxidant activities. Therefore, we engineered MSC-Exos loaded with Ber (Exos-Ber) to enhance the solubility and bioavailability of Ber and for colon targeting, revealing a novel approach for treating UC with natural compounds. Structurally and functionally, Exos-Ber closely resembled unmodified Exos. Both in vitro and in vivo investigations confirmed the antioxidant and anti-inflammatory properties of Exos-Ber. Notably, Exos-Ber exhibited reparative effects on injured epithelial cells and reduced cellular apoptosis. Furthermore, Exos-Ber concurrently demonstrated anti-inflammatory and antioxidant activities, contributing to the mitigation of UC, possibly through its modulation of the MAPK signaling pathway. Overall, our findings demonstrate the potential of Exos-Ber as a promising therapeutic option for alleviating UC, highlighting its capacity to enhance the clinical applicability of Ber. [ABSTRACT FROM AUTHOR]

Background and Aims It is uncertain whether ulcerative colitis leads to accumulated bowel damage on cross-sectional image. We aimed to characterise bowel damage in patients with ulcerative colitis using magnetic resonance imaging [MRI], and to determine its relation with duration of disease and the impact on patients' quality of life. Methods In this prospective study, patients with ulcerative colitis [UC] in endoscopic remission underwent MRI without bowel cleansing, and completed quality-of-life questionnaires. Participants' magnetic resonance findings were analysed considering normal values and thresholds determined in controls with no history of inflammatory bowel disease [ n =40], and in patients with Crohn's disease with no history of colonic involvement [ n  = 12]. Subjects with UC were stratified according to disease duration [< 7 years vs 7‒14 years vs > 14 years]. Results We analysed 41 subjects with ulcerative colitis [20 women; Mayo endoscopic subscore 0 in 38 [92.7%] and 1 in three [7.3%]]. Paired segment-by-segment comparison of magnetic resonance findings in colonic segments documented as being affected by ulcerative colitis versus controls showed that patients with ulcerative colitis had decreased cross-sectional area [ p  ≤ 0.0034] and perimeter [ p  ≤ 0.0005] and increased wall thickness [ p  = 0.026] in all segments. Colon damage, defined as wall thickness ≥ 3 mm, was seen in 22 [53.7%] patients. Colon damage was not associated with disease duration or quality of life. Conclusions Morphological abnormalities in the colon were highly prevalent in patients with ulcerative colitis in the absence of inflammation. Structural bowel damage was not associated with disease duration or quality of life. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease [IBD] patients are at increased risk of developing colorectal neoplasia [CRN]. In this review, we aim to provide an up-to-date overview and future perspectives on CRN management in IBD. Advances in endoscopic surveillance and resection techniques have resulted in a shift towards endoscopic management of neoplastic lesions in place of surgery. Endoscopic treatment is recommended for all CRN if complete resection is feasible. Standard [cold snare] polypectomy, endoscopic mucosal resection and endoscopic submucosal dissection should be performed depending on lesion complexity [size, delineation, morphology, surface architecture, submucosal fibrosis/invasion] to maximise the likelihood of complete resection. If complete resection is not feasible, surgical treatment options should be discussed by a multidisciplinary team. Whereas [sub]total and proctocolectomy play an important role in management of endoscopically unresectable CRN, partial colectomy may be considered in a subgroup of patients in endoscopic remission with limited disease extent without other CRN risk factors. High synchronous and metachronous CRN rates warrant careful mucosal visualisation with shortened intervals for at least 5 years after treatment of CRN. [ABSTRACT FROM AUTHOR]

Background Both vedolizumab and ustekinumab can be considered for the treatment of ulcerative colitis [UC], but head-to-head trials are lacking. Aim We aimed to compare the effectiveness of vedolizumab and ustekinumab after anti-tumour necrosis factor [anti-TNF] failure in UC patients. Patients and Methods In this multicentre study, we included consecutive adult patients with UC, with partial Mayo score >2 and prior anti-TNF exposure, treated with vedolizumab or ustekinumab between January 2019 and August 2022. Comparisons were performed using propensity score analyses [inverse probability of treatment weighting]. Results Among a total of 293 patients included, 151 and 142 received vedolizumab and ustekinumab, respectively. After propensity score analysis, steroid-free clinical remission [SFCR] [partial Mayo score ≤2] was achieved at week 16 in 38.0% and 40.3% of patients treated with vedolizumab and ustekinumab, respectively (adjusted odds ratio [aOR] = 1.11, 95% confidence interval [0.39–3.13], p  = 0.85). Rates of SFCR in patients exposed to one, two, and three lines of biologics/small molecules among patients treated with vedolizumab and ustekinumab were respectively 53.3% vs 62.1% [ p  = 0.52], 44.4% vs 33.8% [ p  = 0.52], and 2.6% vs 19.1% [ p  = 0.027]. Endoscopic remission [SFCR and endoscopic Mayo score ≤1] and histological remission [SFCR, endoscopic remission, and Nancy histological index ≤1] at week 16 were achieved in respectively 5.3% vs 17.5% (aOR = 3.77 [1.25–11.36], p  = 0.018) and 2.1% vs 11.1% (aOR = 5.85 [1.47–23.30], p  = 0.012) in the vedolizumab and ustekinumab groups. No difference regarding the risk of drug discontinuation between the two groups (aHR = 1.03 [0.51–2.08], p  = 0.92) was observed. While no factor was identified for vedolizumab, primary failure to at least one biologic/small molecule (OR = 0.31 [0.11–0.82], p  = 0.018) was significantly associated with a decreased rate of SFCR among patients treated with ustekinumab. Conclusion While no difference in terms of short-term clinical remission was observed, ustekinumab appears to be more effective than vedolizumab in inducing endoscopic and histological remission at week 16 after failure of anti-TNFs in UC. [ABSTRACT FROM AUTHOR]

Background and Aims Several faecal microbial transplantation [FMT] approaches for ulcerative colitis [UC] have been investigated with conflicting results. We have recently published the clinical outcomes from the CRAFT UC Trial using FMT with the UC Exclusion Diet [UCED], compared with FMT alone. Here we aimed to compare the two FMT strategies in terms of microbial profile and function. Methods Subjects recruited to the CRAFT UC study with available pre- and post-intervention faecal samples were included. Donors received diet conditioning for 14 days based on the UCED principles. Group 1 received single FMT by colonoscopy [Day 1] and enemas [Days 2 and 14] without donors' dietary conditioning [ N = 11]. Group 2 received FMT but with donors' dietary pre-conditioning and UCED for the patients [ N  = 10]. Faecal samples were assessed by DNA shotgun metagenomic sequencing. Results Following diet conditioning, donors showed depletion in metabolic pathways involved in biosynthesis of sulphur-containing amino acids. Only Group 2 showed significant shifts towards the donors' microbial composition [ADONIS: R 2 = 0.15, p  = 0.008] and significantly increased Eubacterium AF228LB post-intervention [β-coefficient 2.66, 95% confidence interval 2.1–3.3, q  < 0.05] which was inversely correlated with faecal calprotectin [rho = −0.52, p  = 0.035]. Moreover, pathways involved in gut inflammation and barrier function including branched chain amino acids were enriched post-intervention in Group 2 and were significantly inversely correlated with faecal calprotectin. Conclusion FMT from diet conditioned donors followed by the UCED led to microbial alterations associated with favourable microbial profiles which correlated with decreased faecal calprotectin. Our findings support further exploration of the additive benefit of dietary intervention for both donors and patients undergoing FMT as a potential treatment of UC. [ABSTRACT FROM AUTHOR]

Background and Aims Infections are a safety concern in patients with ulcerative colitis [UC]. Etrasimod is an oral, once daily [QD], selective sphingosine 1-phosphate [S1P]1,4,5 receptor modulator for the treatment of moderately to severely active UC. It leads to selective and reversible lymphocyte sequestration and partial peripheral lymphocyte count decrease. We report infection events from the phase 3 ELEVATE programme. Methods Proportions, incidence rates [IRs; per 100 patient-years], and descriptive analyses of all serious, severe, herpes zoster and opportunistic infections are reported in the Pivotal UC cohort [ELEVATE UC 52 and ELEVATE UC 12]. Cox regression models evaluated potential baseline risk factors. Results In this analysis [ n  = 787], proportions [IRs] of all infection events were similar for patients receiving etrasimod 2 mg QD (18.8% [41.1]) or placebo (17.7% [49.0]). Serious infections occurred in three [0.6%] and five [1.9%] patients receiving etrasimod and placebo, respectively. Two herpes zoster events were reported in each group [etrasimod: 0.4%; placebo: 0.8%], all localised and non-serious. One opportunistic infection event was reported in each group. No patient with an absolute lymphocyte count [ALC] < 0.2 × 109/L reported serious/severe or opportunistic infections; no baseline risk factors were identified for such events. No deaths occurred. Conclusions Patients receiving etrasimod demonstrated no increased risk of infection. The incidence of serious infections and herpes zoster was similar in each group. Among patients receiving etrasimod, no association between ALC < 0.5 × 109/L and infection events was observed. Longer-term follow-up will further characterise the etrasimod safety profile. Clinicaltrials.gov: NCT03945188; NCT03996369 [ABSTRACT FROM AUTHOR]

Paediatric inflammatory bowel disease (PIBD), consisting of Crohn's disease, ulcerative colitis and inflammatory bowel disease unclassified, is a spectrum of chronic inflammatory conditions associated with significant morbidity. The incidence of PIBD continues to increase and disease phenotype is more severe than adult-onset disease. Referral to specialist services and diagnosis of PIBD can be slow; and faecal calprotectin is an invaluable tool for the prioritization of further investigation. Greater understanding of pre-existing treatments (such as anti-TNF monoclonal antibody therapy) and a growing arsenal of biologic and small molecule drugs have brought about significant changes in disease management. Whilst important challenges remain in the longer-term treatment of PIBD, including growth, nutrition and management of refractory disease, there remains a strong research focus on understanding underlying disease pathogenesis and a move towards personalized medicine. This review describes investigations, diagnosis and management of PIBD and presents contemporary evidence on nutritional and medical management. [ABSTRACT FROM AUTHOR]

CT-P13 subcutaneous (SC), an SC formulation of the intravenous (IV) infliximab biosimilar CT-P13 IV, creates a unique exposure profile. The LIBERTY studies aimed to demonstrate superiority of CT-P13 SC vs placebo as maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC). Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately to severely active CD or UC and inadequate response or intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks 0, 2, and 6. At week 10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until week 54 (maintenance phase) using prefilled syringes. (Co-) primary end points were clinical remission and endoscopic response (CD) and clinical remission (UC) at week 54 (all-randomized population). Overall, 396 patients with CD and 548 patients with UC received induction treatment. At week 54 in the CD study, statistically significant higher proportions of CT-P13 SC–treated patients vs placebo-treated patients achieved clinical remission (62.3% vs 32.1%; P <.0001) and endoscopic response (51.1% vs 17.9%; P <.0001). In the UC study, clinical remission rates at week 54 were statistically significantly higher with CT-P13 SC vs placebo (43.2% vs 20.8%; P <.0001). Achievement of key secondary end points was significantly higher with CT-P13 SC vs placebo across both studies. CT-P13 SC was well tolerated, with no new safety signals identified. CT-P13 SC was more effective than placebo as maintenance therapy and was well tolerated in patients with moderately to severely active CD or UC who responded to CT-P13 IV induction. ClinicalTrials.gov , Numbers: NCT03945019 (CD) and NCT04205643 (UC). CT-P13 (infliximab, an anti–tumor necrosis factor therapy) is a biologic drug injected under the skin (ie, subcutaneously). Subcutaneous CT-P13 was more effective than a placebo and well tolerated in patients with moderate to severe Crohn's disease or ulcerative colitis. [ABSTRACT FROM AUTHOR]

TGF-β1 induces epithelial-mesenchymal transition (EMT) and leads to intestinal fibrosis in ulcerative colitis (UC). We aimed to investigate the expression of transcribed ultraconserved region uc.290 in chronic UC and its role in intestinal fibrosis. Colon specimens were taken from thirty chronic active UC, chronic inactive UC and healthy controls respectively. Modified Mayo score, expressions of uc.290, TGF-β1, EMT biomarkers (Vimentin, α-SMA and E-cadherin) and intestinal fibrosis biomarker (collagen Ⅲ) in colon biopsy specimens were determined in human. Expressions of TGF-β1, EMT biomarkers and collagen Ⅲ were determined in uc.290 overexpressed or silenced epithelial colon cells (HT29). Uc.290, TGF-β1 and collagen Ⅲ were overexpressed, and EMT was prominent in chronic active UC. Uc.290 level had a positive correlation with modified Mayo score in chronic active UC. TGF-β1 and collagen Ⅲ were overexpressed, and EMT was prominent in uc.290 overexpressed HT29 cells. Uc.290 was overexpressed in chronic active UC and might promote intestinal fibrosis by TGF-β1/EMT/collagen Ⅲ pathway. [ABSTRACT FROM AUTHOR]

The article focuses on the evolving role of Janus kinase (JAK) inhibitors in treating inflammatory bowel disease (IBD), highlighting their efficacy and safety concerns. It discusses healthcare providers' perceptions of cardiovascular risks and recent approvals for JAK inhibitors in ulcerative colitis and Crohn's disease, emphasizing the need for monitoring patient outcomes amid potential risks.

Aims/Background Accurate prediction of recurrence after treatment is crucial for controlling the progression and improving the prognosis of active ulcerative colitis (UC) patients. Previous studies have evaluated the therapeutic response in UC patients by assessing mucosal healing, using measures such as the Paddington International Virtual ChromoendoScopy Score (PICaSSO) and the PICaSSO Histological Remission Index (PHRI). The PHRI is effective for evaluating treatment response and disease control in UC patients, but its predictive value for short-term recurrence has not been reported in the literature. Therefore, this retrospective analysis of clinical data aims to explore the predictive value of the PHRI and provide a reference for improving the prognosis of UC patients. Methods Clinical data of UC patients in clinical remission admitted to our hospital from June 2017 to June 2023 were retrospectively collected. Patients were divided into the recurrence group and the non-recurrence group, based on whether they experienced recurrence during the one-year follow-up. Clinical data, laboratory test results, and PHRI scores were collected. Variables that showed statistically significant differences between groups in univariate analysis were included in multivariate logistic regression analysis. The predictive value of PHRI was analyzed with receiver operating characteristic (ROC) curve analysis. Results One hundred and two UC patients in the clinical remission stage were included in this study, and there were no cases of loss to follow-up. Among them, 36 patients (35.29%) experienced recurrence within the one-year follow-up, whereas 66 patients (64.71%) did not. Compared with the non-recurrence group, the recurrence group had a more number of cases with lesions in the left-sided colon and extensive colon, higher percentages of cases that were moderate or severe, and a significantly higher colonoscopy score (p < 0.05). Compared with the non-recurrence group, the PHRI score of the recurrence group was significantly higher (p < 0.001). Multivariate logistic regression analysis showed that that the lesion range (OR = 4.127, p = 0.005), disease severity (OR = 3.889, p = 0.019), colonoscopy score (OR = 6.128, p < 0.001), and PHRI score (OR = 5.466, p < 0.001) were independent risk factors for recurrence in UC patients. The results of ROC curve analysis showed that the area under the curve of the PHRI score in predicting the recurrence of UC patients was 0.838 (95% CI: 0.760–0.916). When the optimal cut-off value was 1 point, the sensitivity and specificity were the highest, which were 89.58% and 65.58%, respectively, indicating that PHRI score had good predictive value. Conclusion The lesion extent, disease severity, endoscopic score, and PHRI score are associated with recurrence within one year in UC patients in the clinical remission stage, and the PHRI score has good predictive value. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is associated with multiple factors that influence bone metabolism. This study aimed to compare the clinical manifestations and diagnostic parameters of patients with Crohn's disease (CD) and ulcerative colitis (UC) at the time of diagnosis, as well as to assess their relationship with subsequent bone disorders. Methods: Blood tests (including calcium–phosphate metabolism) and fecal tests (including calprotectin) were performed in eighty children recently diagnosed with IBD. Additionally, the bone densitometry results were evaluated in 25 of them. Results: Diarrhea (p = 0.02) and bloody stools (p < 0.001) were more frequent in patients with UC, whereas fever was more common in patients with CD (p = 0.003). Laboratory tests revealed anemia in 62.5% (50/80) and thrombocytosis in 36.3% (29/80). Higher calprotectin levels in the feces were found in girls at the time of diagnosis (p = 0.02). Osteopenia was detected in almost half of the examined patients (12/25), and 20% (5/25) met the criteria for osteoporosis. Low calcium levels at diagnosis were correlated with subsequent bone disorders (p = 0.005). Insufficient levels of vitamin D were detected in 77.8% (56/80). Conclusions: Early disease detection and the appropriate monitoring of children with IBD may decrease the risk of serious consequences, including osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Didymin is a dietary flavonoid derived from citrus fruits and has been shown to have extensive biological functions, especially anti-inflammatory effects, but its mechanism is unclear. The purpose of this study was to investigate the potential mechanism of didymin that alleviates ulcerative colitis. Methods and Results: Our results indicated that didymin could alleviate the symptoms of ulcerative colitis, as it inhibited the expressions of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Didymin also promoted the expressions of claudin-1 and zona occludens-1(ZO-1), which are closely related with restoring colon barrier function. Didymin also increased the abundance of Firmicutes and Verrucomicobiota, while decreasing the abundance of Bacteroidota and Proteobacteria. Meanwhile, didymin significantly altered the levels of metabolites related to arginine synthesis and metabolism, and lysine degradation in the colitis mice. Utilizing network pharmacology and molecular docking, our results showed that the metabolites L-ornithine and saccharin could interact with signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-B (NF-κB). In this in vitro study, L-ornithine could reduce the expressions of transcription factors STAT3 and NF-κB, and it also inhibited the expressions of IL-6 and IL-1β in the lipopolysaccharides (LPS) induced in RAW264.7 cells, while saccharin had the opposite effect. Conclusions: Taken together, didymin can regulate gut microbiota and alter metabolite products, which can modulate STAT3 and NF-κB pathways and inhibit the expressions of inflammatory factors and inflammatory response in the DSS-induced colitis mice. [ABSTRACT FROM AUTHOR]

Background and Aim: Inflammatory bowel disease (IBD) is a progressive condition where ongoing inflammation in the gastrointestinal tract can lead to complications such as strictures, and fistulae. The long‐term outcomes of newly diagnosed patients under current medical therapy can be used to plan health service provision and guide patients. Methods: Prospective population‐based data on all incident patients diagnosed with IBD in Canterbury was gathered in 2014 (n = 205). The medical records of these patients were followed for medication use, disease progression, hospitalization, surgery and mortality, in the 10 years since their diagnosis. Survival analysis and cox regression determined characteristics associated with earlier time to these outcomes. Results: Medical records of 184 IBD patients were able to be retrieved. Immunomodulators were used by 62% and biologics by 35%; hospitalization occurred for 42% and surgery for 15%. Montreal phenotype progression occurred for 21 and 7% of the cohort died. Younger age at diagnosis hazard ratio (HR) 2.1 (95% confidence interval [CI] 1.1–4.0) and Crohn's disease HR 1.7 (95% CI 1.1–2.6) was associated with immunomodulator use. Younger age was also associated with biologic use HR 2.9 (95% CI 1.2–6.9). Male gender was associated with surgery HR 2.8 (95% CI 1.2–6.4). Perianal disease at diagnosis (14.7%) was associated with immunomodulator use HR 2.58 (95% CI 1.44–4.59) and Montreal phenotype progression HR 2.93 (95% CI 1.10–7.77). Conclusion: In the 10 years since diagnosis disease progression and treatment escalation occurred for most of this population‐based cohort. Earlier intervention for patients with higher‐risk characteristics may improve long‐term outcomes reducing the burden on health systems. [ABSTRACT FROM AUTHOR]

Fasciola hepatica is a liver fluke that resides in the bile ducts of various mammals. The parasitosis leads to economic losses in animal production estimated at USD 3.2 billion annually. It is also considered a zoonosis of great significance and a problem for public health affecting 2.4 million people worldwide. Nevertheless, besides the negative aspects of infestation, the antigens released by the fluke, F. hepatica Excretory-Secretory Products (Fh-ES) contain several immunomodulatory molecules that may be beneficial during the course of type I diabetes, multiple sclerosis, ulcerative colitis, or septic shock. This phenomenon is based on the natural abilities of adult F. hepatica to suppress proinflammatory responses. To underline the molecular basis of these mechanisms and determine the role of microRNA (miRNA) in the process, lipopolysaccharide (LPS)-activated THP-1 macrophages were stimulated with Fh-ES, followed by miRNA microarray analyses. Surprisingly, no results indicating changes in the miRNA expression profile were noted (p < 0.05). We discuss potential reasons for these results, which may be due to insufficient sensitivity to detect slight changes in miRNA expression or the possibility that these changes are not regulated by miRNA. Despite the negative data, this work may contribute to the future planning of experiments by other researchers. [ABSTRACT FROM AUTHOR]

Background/Objectives: In this study, serum selenium levels in patients with Crohn's disease (CD) and ulcerative colitis (UC) were evaluated to identify potential predictive markers of disease activity. Conducted in 100 inflammatory bowel disease (IBD) patients (54 CD, 46 UC) and 100 healthy controls, this research provides novel insights through focusing on the regional selenium status of people with IBD in the Polish population, a demographic with limited existing data. Methods: Selenium concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). Results: Significantly lower levels of selenium were observed in CD (64.79 µg/L ± 12.15 µg/L) and UC (68.61 µg/L ± 11.43 µg/L) patients when compared with the controls (90.52 ± 12.00 µg/L, p < 0.0001). Regression analysis identified leukocyte and erythrocyte counts and bilirubin as significant predictors of selenium levels in UC patients, while no significant predictors were found for CD. Conclusions: The findings suggest that selenium deficiency is linked to IBD and may serve as a non-invasive biomarker for disease severity, particularly in UC. This practical approach offers a potential alternative to invasive procedures such as endoscopy for monitoring disease progression. However, further research is needed to confirm these findings in larger populations and explore the therapeutic role of selenium supplementation in IBD management. [ABSTRACT FROM AUTHOR]

This study investigated the effects of solid-state fermentation with Clostridium butyricum on the microstructure of wheat bran, the release of dietary fiber and phenolic compounds, and antioxidant capacity. Compared with unfermented wheat bran, insoluble dietary fiber and phytic acid content decreased, whereas soluble dietary fiber and water-extractable arabinoxylan content increased in C. butyricum culture. Because of the increased release of phenolic compounds, such as ferulic acid and apigenin, and organic acids, such as isobutyric acid, the antioxidant capacity of the culture was considerably improved. Furthermore, the culture of C. butyricum treated with dextran sulfate sodium-induced ulcerative colitis in mice enhanced the expression of intestinal mucus and tight-junction proteins, modulating the gut microbiota structure, increasing the levels of short-chain fatty acids in the intestine, and restoring the essential functions of the gut microbiota. These anti-inflammatory effects stemmed from the combined action of various effective components. [ABSTRACT FROM AUTHOR]

Malondialdehyde (MDA) is a naturally occurring organic compound produced as a byproduct of lipid peroxidation. It serves as one of the most widely recognized biomarkers for oxidative stress. Elevated levels of MDA have been observed in patients with inflammatory bowel disease (IBD), suggesting its involvement in the pathogenesis and progression of the disease. In this study, we analyzed MDA levels within a well-characterized and extensive cohort of IBD patients. Our objective was to investigate the association between MDA levels and disease characteristics in this population. This is a cross-sectional study that encompassed 197 patients with IBD. Multivariable linear regression analysis was performed to study the relationship between disease characteristics and circulating MDA. MDA was significantly associated with male sex in IBD patients but not with other demographic characteristics or classic cardiovascular risk factors. Regarding disease features such as phenotype or activity indices, their relationship with MDA was scarce. Several lipid profile molecules showed a significant association with MDA levels after multivariable analysis. Similarly, the liver fibrosis-4 index and hepatic elastography values were significantly related to higher MDA levels after adjusting for covariates. In conclusion, the sources of elevated MDA in IBD are primarily linked to lipid profile abnormalities and liver disease. [ABSTRACT FROM AUTHOR]

Purpose of Review: Transition of care for pediatric patients with inflammatory bowel diseases (IBD) is a continuous, dynamic process that takes place over several years with a coordinated approach executed by a multidisciplinary team. We review the concepts, tools, and research in effective transitioning and transfer of care for adolescent/young adult patients with IBD. Recent Findings: Given the constraints within the healthcare system, effective transitioning can be challenging to implement in everyday clinical practice. Different barriers include resources and expertise in effective transitioning by pediatric and adult gastroenterology healthcare providers and the impact of non-gastrointestinal issues facing young adult patients who are learning to manage and coordinate all aspects of their medical care and health maintenance. Factors that facilitate successful care transitioning and transfer include structured transitioning programs, utilization of validated transition checklists, and IBD medical summaries. Summary: Proactive transitioning by pediatric gastroenterologists in partnership with their emerging young adult patients with IBD leads to better clinical and psychosocial outcomes and ultimately, effective transfer of care to adult gastroenterology. By utilizing utilize comprehensive transition assessment tools and medical summaries in partnership with their patients, pediatric and adult gastroenterology teams can better prepare patients as they transfer to independent care and health maintenance. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC), which is linked to chronic oxidative stress, has been on the rise in Japan, attributed to the recent Westernization of dietary habits. Sulforaphane, which is abundant in broccoli sprouts (BS), has been shown to enhance antioxidant activity by up-regulating nrf2-mediated antioxidant enzymes. We have previously shown that the dietary intake of sulforaphane-rich broccoli sprouts mitigates H.pylori-induced gastritis not only by enhancing nrf2-dependent anti-oxidant activity against oxidative stress from H.pylori infection, but also by directly inhibiting H.pylori activity (Cancer Prev Res 2:353-360,2009). In this study, we examined if the dietary approach with BS affects intestinal microbiota, thereby mitigating colonic inflammation in mesalazine-treated human UC patients. Objective: In this study, we examined if dietary intake of sulforaphane-rich broccoli sprouts decreases fecal calprotectin levels in patients with ulcerative colitis Methods: This study was registered with the University hospital Medical Information Network (UMIN) in Japan under the Clinical Trial Registration Number, UMIN000041972. Twenty-eight mild UC patients treated with mesalazine were divided between the sulforaphane-rich BS group (n=14) or the sulforaphane-free alfalfa sprouts (AS) group (n=14). These subjects were instructed to take 20 g of raw BS or AS daily for 8 weeks, with BS containing 4.4 mg/g glucoraphanin, a precursor of sulforaphane, and AS containing no glucoraphanin. Stool samples were obtained just before and after the 8 weeks sprouts treatment. Levels of fecal calprotectin were measured as the quantitative indices for colonic mucosal inflammation. We conducted an examination of gut bacteria through a method called terminal restriction fragment length polymorphism (TR-FLP) analysis of fecal samples. Results: 1. Twelve patients from the BS group and 11 from the AS group completed the intervention study as requested. 2. Only the treatment with BS caused a significant decrease in the level of fecal calprotectin as well as an increase in the fecal component of Clostridium subcluster IV and XIVa, which have been reported to enhance butyrate production. 3. There was no change in the clinical activity index after intake of either the BS or the AS. Conclusion: These results indicate that dietary approach with sulforaphane-rich BS mitigates colonic inflammation in mesalazine-treated UC patients. Our data also suggest that the beneficial effects of the BS may be related with the increase in butyrate-producing intestinal microbiota by dietary approach with sulforaphane. [ABSTRACT FROM AUTHOR]

Background: Observational studies have indicated that peripheral blood eosinophil count is elevated in individuals diagnosed with ulcerative colitis (UC) and correlates with the disease activity of UC. However, this conclusion contradicts with findings from other studies. Therefore, we employed Mendelian randomization (MR) method to assess the genetic link between eosinophil count and UC. Method: This MR study utilized summary data from genome‐wide association studies (GWAS) on eosinophil count and UC. The main approach used for conducting MR analysis was the inverse variance weighted (IVW) method. Meta‐analysis of the IVW results was performed alongside multiple sensitivity analyses to confirm the robustness of the MR analysis results. Results: The IVW method unveiled a causal relationship between eosinophil count and UC (OR = 1.18, 95% CI: 1.04–1.33, p =.01) in the discovery cohort. This finding was further corroborated by the replication cohorts (OR = 1.16, 95% CI: 1.04–1.29, p =.01; OR = 1.12, 95% CI: 1.01–1.24, p =.03). The meta‐analysis indicated that the overall odds ratio (OR) for all studies was 1.15 (common effect model, 95% CI: 1.08–1.23, p <.01). Sensitivity analysis suggested the absence of heterogeneity and horizontal pleiotropy in all MR analyses. Conclusion: Based on bidirectional two‐sample MR analysis, there is an indication that elevated eosinophil count may increase the risk of UC. However, potential confounding factors cannot be ruled out, and further research is necessary to explore how eosinophils contribute to the onset and progression of UC. [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin (mTOR) pathway plays a key role in determining immune cells function through modulation of their metabolic status. By specific deletion of Rictor in CD11c+ myeloid cells (referred to here as CD11cRicΔ/Δ), we investigated the role of mTOR complex 2 (mTORC2) signaling in dendritic cells (DCs) function in mice. We showed that upon dextran sulfate sodium–induced colitis, the lack of mTORC2 signaling CD11c+ cells diminishes the colitis score and abrogates DC migration to the mesenteric lymph nodes, thereby diminishing the infiltration of T helper 17 cells in the lamina propria and subsequent inflammation. These findings corroborate with the abrogation of cytoskeleton organization and the decreased activation of Rac1 and Cdc42 GTPases observed in CD11c+-mTORC2–deficient cells. Meta-analysis on colonic samples from ulcerative colitis patients revealed increased gene expression of proinflammatory cytokines, which coincided with augmented expression of the mTOR pathway, a positive correlation between the DC marker ITGAX and interleukin-6, the expression of RICTOR, and CDC42. Together, this work proposes that targeting mTORC2 on DCs offers a key to hamper inflammatory responses, and this way, ameliorates the progression and severity of intestinal inflammatory diseases. [ABSTRACT FROM AUTHOR]

This study was to investigate the effects of the polysaccharides (PPM60−III) and sulfated polysaccharides (SPPM60−III) of pine pollen on the Th17/Treg balance, inflammatory cytokines, intestinal microbiota, and metabolite distribution in 3% DSS drinking water-induced UC mice. First of all, the physiological results showed that PPM60−III and SPPM60−III could alleviate UC, which was shown by the reduction in liver Treg cells, the rebalance of Th17/Treg, and the modulation of inflammatory cytokines. In addition, the 16S rRNA results showed that PPM60−III and SPPM60−III could decrease Beijerinck and Bifidobacterium, and increase Akkermansia, Escherichia coli, and Fidobacteria. Finally, the metabonomics results showed that PPM60−III and SPPM60−III also restored purine and glycerolipid metabolism, up-regulated nicotinate and nicotinamide metabolism and caffeine metabolism to inhibit inflammation. In conclusion, PPM60−III and SPPM60−III could inhibit UC by regulating gut bacteria composition and metabolite distribution; SPPM60−III showed better anti-colitis activity. [ABSTRACT FROM AUTHOR]

Background: Antibiotic exposure has been reported as a risk factor for the development of ulcerative colitis; however, the clinical results were controversial. Therefore, we performed a meta-analysis to evaluate the association of antibiotic exposure with the new onset of UC. Methods: A comprehensive literature search for relevant studies published up to February 2024, exploring the association between antibiotic exposure and new-onset UC, was performed by using Medline and Embase, and the statistical analysis was conducted by using the Stata software. Results: A total of 16 articles were included in the study, including 12 case-control studies and 4 cohort studies. The pooled analysis revealed that antibiotic exposure was associated with an increased risk of new-onset UC (summary OR = 1.28, 95% CI = 1.26 - 1.31). Subgroup analyses showed that both case-control studies and cohort studies have yielded consistent conclusions. Conclusions: This meta-analysis suggests that antibiotic exposure is a risk factor for the development of UC. It is, therefore, necessary to avoid unnecessary and excessive use of antibiotics. [ABSTRACT FROM AUTHOR]

Background/Objectives: Isatidis Folium (IF) has been used in traditional medicine for various ailments, and recent research highlights its anti-inflammatory, antiviral, and detoxifying properties. This study investigated the anti-inflammatory effects of a hydroethanolic extract of IF (EIF) on inflammasomes and colitis. Methods: Dextran sulfate sodium (DSS)-induced colitis model C57BL/6 mice were treated with DSS, mesalamine, or EIF (200 mg/kg). Parameters such as daily disease activity index (DAI), spleen weight, colon length, and histopathology were evaluated. Intestinal fibrosis, mucin, and tight junction proteins were assessed using Masson's trichrome, periodic acid–Schiff, and immunohistochemistry staining. RAW264.7 and J774a.1 macrophages were treated with EIF and lipopolysaccharide, with cell viability assessed via the cell counting kit-8 assay, nitric oxide (NO) production with Griess reagent, and cytokine levels with the enzyme-linked immunosorbent assay. NF-κB inhibition was analyzed using the luciferase assay, and phytochemical analysis was performed using UPLC-MS/MS. Results: EIF mitigated weight loss, reduced DAI scores, prevented colon shortening, and attenuated mucosal damage, fibrosis, and goblet cell loss while enhancing the tight junction protein occludin. The anti-inflammatory effects of EIF in RAW264.7 cells included reduced NO production, pro-inflammatory cytokines, and NF-κB activity, along with inhibition of NLRP3 inflammasome responses in J774a.1 cells. The key constituents identified were tryptanthrin, indigo, and indirubin. Conclusions: Animal studies demonstrated the efficacy of EIF in alleviating colitis, suggesting its potential for treating inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Diet has been linked to gut dysbiosis and the onset, course, and response to treatment of patients with IBD and metabolic disease. Methods: This single-centre prospective case-control study investigated the relationship between dietary intake, metabolic profile, and stool microbial composition in 57 individuals with IBD in clinical remission and 24 healthy individuals (HC). Participants' baseline anthropometric measurements, serum metabolic parameters, lipid profiles, and oral and stool samples for microbiota testing were collected. Their dietary intake and physical activity were documented. A partially corrected correlation was performed to examine the associations between variables and p-values adjusted for multiple comparisons using the Benjamini–Hochberg equation (adj-p). Results: In participants with IBD, the intake of saturated fat correlated positively, and the intake of dietary fibre correlated negatively with anthropometric indices (saturated fat and BMI: r = 0.37, adj-p = 0.04, fibre and BMI: r = −0.45, adj-p = 0.01). Higher anthropometric indices were associated with poorer glucose control and a less favourable serum lipid profile (BMI and insulin: r = 0.48, p < 0.01, WHR and triglycerides: r = 0.57, p < 0.01). The stool microbiota of participants in the IBD group was less diverse and more similar to their oral microbiota than was observed in the HC group (Mann–Whitney U test p = 0.03). Within the IBD group, a higher intake of added sugar and processed meat and a higher serum insulin level was associated with lower stool microbial alpha diversity (processed meat intake and Shannon's diversity: r = −0.43, adj-p = 0.02; added sugar and Shannon's diversity: r = −0.39, adj-p = 0.03; insulin and Shannon's diversity: r = −0.45, adj-p = 0.02). Neither the dietary intake nor stool microbial composition correlated with the risk of disease flaring. Conclusions: Our findings suggest that dietary intake is associated with the metabolic health and gut microbial composition of IBD patients. [ABSTRACT FROM AUTHOR]

Multi-methods have been developed to control ulcerative colitis. This research targeted to probe that lentinan combined with probiotics suppresses inflammation and oxidative stress responses in a dextran sulfate sodium (DSS)-induced colitis model. A mouse model of colitis was induced through oral administration with 2.5% DSS and treated with lentinan and probiotics independently or in combination. Then, bodyweight and Disease Activity Index (DAI) of mice were determined. Histopathology of colon tissue was analyzed, and apoptosis, inflammation and oxidative stress in the colon tissue of mice were observed. An HT-29 cell model of colitis was established by DSS stimulation and cultured with lentinan and/or probiotics to examine cell proliferation and apoptosis. The data discovered that after DSS induction of colitis, mice developed weight loss, increased DAI score, and shortened the length of colon. Also, severe histopathology of the colon, and increased apoptosis, inflammation and oxidative stress were recognizable. Lentinan could alleviate DSS-induced colitis, and the highest dose was the most significant. Probiotics could also relieve UC in mice, and mixed probiotics had a better therapeutic effect than single probiotics. Lentinan combined with probiotics could further alleviate DSS-induced colitis damage. In addition, lentinan combined with probiotics impaired apoptosis and enhanced proliferation of DSS-treated HT-29 cells. In a word, lentinan combined with probiotics reduces the inflammatory response and oxidative stress of UC. [ABSTRACT FROM AUTHOR]

Patients with inflammatory bowel disease (IBD) are at an increased risk of developing colitis-associated neoplasia (CAN), including colorectal cancer (CRC), through the inflammation-dysplasia-neoplasia pathway. Dysplasia is the most reliable, early and actionable marker for CAN in these patients. While such lesions are frequently encountered, adequate management depends on an accurate assessment, complete resection and close surveillance. With recent advances in endoscopic technologies and research in the field of CAN, the management of dysplastic lesions has significantly improved. The American Gastroenterology Association and Surveillance for Colorectal Endoscopic Neoplasia Detection (SCENIC) provide a guideline framework for approaching dysplastic lesions in patients with IBD. However, there are significant gaps in these recommendations and real-world clinical practice. Accurate lesion assessment remains pivotal for adequate management of CAN. Artificial intelligence-guided modalities are now increasingly being used to aid the detection of these lesions further. As the lesion detection technologies are improving, our armamentarium of resection techniques is also expanding and includes hot or cold polypectomy, endoscopic mucosal resection, endoscopic sub-mucosal dissection and full-thickness resection. With the broadened scope of endoscopic resection, the recommendations regarding surveillance after resection has also changed. Certain patient populations such as those with invisible dysplasia or with prior colectomy and ileal pouch anal anastomosis need special consideration. In the present review, we aim to provide a state-of-the-art summary of the current practice of endoscopic detection, resection and surveillance of dysplasia in patients with IBD and provide some perspective on the future directions based on the latest research. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a debilitating chronic disease marked by persistent inflammation and intestinal fibrosis. Despite the availability of various treatments, many patients fail to achieve long-term remission, underscoring a significant unmet therapeutic need. BMS-477118, a reversible inhibitor of dipeptidyl peptidase 4 (DPP4), has demonstrated anti-inflammatory properties in preclinical and clinical studies with minimal adverse effects compared to other antidiabetic agents. However, the potential benefits of BMS-477118 in chronic UC have not yet been explored. In this study, we aimed to investigate the effects of BMS-477118 in rats subjected to chronic dextran sodium sulfate (DSS) administration. Our findings indicate that BMS-477118 activates the interconnected positive feedback loop involving AMPK, SIRT1, and FOXO3a, improving histological appearance in injured rat colons. BMS-477118 also reduced fibrotic changes associated with the chronic nature of the animal model, alleviated macroscopic damage and disease severity, and improved the colon weight-to-length ratio. Additionally, BMS-477118 prevented DSS-induced weight loss and enhanced tight junction proteins. These effects, in conjunction with reduced oxidative stress and its potential anti-inflammatory, antiapoptotic, and autophagy-inducing properties, fostered prolonged survival in rats with chronic UC. To conclude, BMS-477118 has the potential to activate the AMPK/SIRT1/FOXO3a signaling pathway in inflamed colons. These results suggest that the AMPK/SIRT1/FOXO3a pathway could be a new therapeutic target for UC. Further research is mandatory to explore the therapeutic possibilities of this pathway. Additionally, continued studies on the therapeutic potential of BMS-477118 and other DPP4 inhibitors are promising for creating new treatments for various conditions, including UC in diabetic patients. [ABSTRACT FROM AUTHOR]

Introduction: The rapid advancement of science and technology has significantly expanded the capabilities of artificial intelligence, enhancing diagnostic accuracy for gastric cancer. Methods: This research aims to utilize endoscopic images to identify various gastric disorders using an advanced Convolutional Neural Network (CNN) model. The Kvasir dataset, comprising images of normal Z-line, normal pylorus, ulcerative colitis, stool, and polyps, was used. Images were pre-processed and graphically analyzed to understand pixel intensity patterns, followed by feature extraction using adaptive thresholding and contour analysis for morphological values. Five deep transfer learning models—NASNetMobile, EfficientNetB5, EfficientNetB6, InceptionV3, DenseNet169—and a hybrid model combining EfficientNetB6 and DenseNet169 were evaluated using various performance metrics. Results & discussion: For the complete images of gastric cancer, EfficientNetB6 computed the top performance with 99.88% accuracy on a loss of 0.049. Additionally, InceptionV3 achieved the highest testing accuracy of 97.94% for detecting normal pylorus, while EfficientNetB6 excelled in detecting ulcerative colitis and normal Z-line with accuracies of 98.8% and 97.85%, respectively. EfficientNetB5 performed best for polyps and stool with accuracies of 98.40% and 96.86%, respectively.The study demonstrates that deep transfer learning techniques can effectively predict and classify different types of gastric cancer at early stages, aiding experts in diagnosis and detection. [ABSTRACT FROM AUTHOR]

Background: Cathepsins, key regulators of the pathology of gastrointestinal disorders such as inflammatory bowel disease (IBD), are a target protease that has attracted much attention in recent years. IBD is a chronic and relapsing inflammatory disorder of the gut. Traditional studies have shown a correlation between cathepsin and the risk of IBD, while the causal relationship remains unclear. Methods: This study utilized Mendelian randomization techniques to evaluate the causal relationships between eleven cathepsins and the subtypes of IBD, such as ulcerative colitis (UC) and Crohn's disease (CD). We also performed a series of sensitivity analyses to validate the primary Mendelian randomization (MR) results, including Cochran's Q test, the MR-PRESSO global test, and the MR pleiotropy test. Results: The forward MR analyses showed no significant association between cathepsins and IBD. Reverse Mendelian randomization analyses suggested that UC might lead to elevated cathepsin G levels [inverse-variance weighted (IVW): p = 0.038, b = 9.966], and CD might cause a decrease in cathepsin B levels [IVW: p = 0.002, b = -10.525] and cathepsin L1 levels [IVW: p = 0.045, b = -4.742]. Conclusions: Our findings offer novel and comprehensive evidence on the impact of UC or CD on cathepsins, potentially providing valuable insights into the treatment and prognosis of IBD. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC), a subtype of inflammatory bowel disease, occasionally manifests with extraintestinal manifestations. We present a 51-year-old male with refractory UC and immune thrombocytopenia (ITP) resistant to conventional treatments. The introduction of biologics, ustekinumab or adalimumab, resulted in clinical remission of colitis and improvements in platelet count. This case underscores the efficacy of biologics in managing refractory UC associated with ITP, emphasizing their potential to control intestinal inflammation and address concurrent thrombocytopenia, potentially avoiding surgical intervention. [ABSTRACT FROM AUTHOR]

Recent studies have reported the occurrence of upper gastrointestinal (UGI) inflammation in patients with ulcerative colitis (UC). However, whether UC-associated UGI and colorectal lesions share pathogenic cytokine profiles and responses to biologics remains unknown. Herein, we report a case of concurrent UC and ulcerative duodenitis (UD) that displayed unique responses to biologic treatment. Although treatment with prednisolone (PSL) failed to induce remission in both disorders, golimumab (GLM) and ustekinumab (UST) were effective against UD and UC, respectively, and remission of both disorders was achieved using UST. Immunofluorescence analyses revealed that numbers of immune cells expressing TNF-α were comparable in both duodenal and rectal mucosa before the treatment. GLM or UST treatment markedly decreased numbers of TNF-α-expressing duodenal immune cells, suggesting the presence of correlation between TNF-α expression and disease activity of UD. In contrast, TNF-α expression was not parallel to disease activity of UC because GLM or PSL failed to induce remission despite a marked reduction in TNF-α expression. Responsiveness to GLM or UST together with immunofluorescence studies suggests that TNF-α and IL-12/23p40 are pathogenic cytokines causing UD and UC, respectively, in the present case. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS), primary sclerosing cholangitis (PSC), and autoimmune pancreatitis (AIP) are known as extraintestinal manifestations (EIMs) of ulcerative colitis (UC). A 74-year-old Japanese man visited our hospital because of white stool. He had been diagnosed with AS when he was 30 years old, and he was HLA-B27-positive. Based on various examination results, it was suspected that AIP had caused bile duct stricture. During the clinical course, he was diagnosed with UC and PSC. Then, AIP was diagnosed because he had localized pancreatic enlargement, irregular stenosis of the main pancreatic duct, PSC, and no tumor cells of pancreas. A patient with all four of these diseases, AS, AIP, PSC, and UC, is very rare. Therefore, we report a quite rare case with three EIMs (AS, PSC, and AIP) of UC. [ABSTRACT FROM AUTHOR]

Objective: To review the pharmacologic and clinical profile of etrasimod in the treatment of ulcerative colitis (UC). Data sources: A PubMed search was conducted from inception to November 2023 using the keywords etrasimod, ulcerative colitis, and sphingosine-1-phosphate receptor modulator. Information was also obtained from published abstracts and package insert. Study selection and data extraction: Phase 2 and 3 studies plus relevant literature on etrasimod pharmacologic and clinical profile were reviewed. Data synthesis: Per ELEVATE, 2 phase 3 studies, a higher proportion of patients with moderately to severely active UC achieved clinical remission in the induction and maintenance phase with etrasimod compared with placebo. In addition, a higher proportion of patients achieved secondary endpoints of clinical response, endoscopic improvement-histologic remission, corticosteroid-free remission, and endoscopic improvement with etrasimod vs placebo. Common adverse events include anemia and headache. Relevance to patient care and clinical practice in comparison with existing drugs: Etrasimod is now the second orally administered sphingosine-1-phosphate modulator approved for UC, providing patients with additional treatment options. Efficacy rates of this treatment are in line with other UC medication options. Similar to other sphingosine-1-phosphate receptor modulators, various assessments are required at baseline and during treatment to ensure safe and appropriate use. Conclusion: Etrasimod is another possibility in the armamentarium of UC treatment, providing patients with more oral medication options. Prior to treatment initiation, several assessments relating to safety, drug interactions, and pharmacogenomics factors are advised. [ABSTRACT FROM AUTHOR]

An oral colon-targeted drug delivery system holds great potential in preventing systemic toxicity and preserving the therapeutic benefits of ulcerative colitis (UC) treatment. In this study, we developed a negatively charged PLGA-PEG nanoparticle system for encapsulating naringin (Nar). Additionally, chitosan and mannose were coated on the surface of these nanoparticles to enhance their mucosal adsorption and macrophage targeting abilities. The resulting nanoparticles, termed MC@Nar-NPs, exhibited excellent resistance against decomposition in the strong acidic gastrointestinal environment and specifically accumulated at inflammatory sites. Upon payload release, MC@Nar-NPs demonstrated remarkable efficacy in alleviating colon inflammation as evidenced by reduced levels of pro-inflammatory cytokines in both blood and colon tissues, as well as the scavenging of reactive oxygen species (ROS) in the colon. This oral nanoparticle delivery system represents a novel approach to treating UC by utilizing Chinese herbal ingredient-based oral delivery and provides a theoretical foundation for local and precise intervention in specific UC treatment. [ABSTRACT FROM AUTHOR]

Upadacitinib is an oral new selective JAK1 inhibitor that has been approved for treating adult patients with moderately to severely active ulcerative colitis. However, a growing number of studies are needed on the effectiveness of upadacitinib in the treatment of acute severe ulcerative colitis. This study was mainly aimed to describe the clinical and endoscopic effectiveness of upadacitinib 45 mg in Chinese acute severe ulcerative colitis patients following eight weeks of treatment. In this study, we examined all patients with acute severe ulcerative colitis from Xijing IBD Center, Xi'an, China, with acute severe ulcerative colitis. All patients were initially given oral upadacitinib 45 mg. Clinical indicators, C-reactive protein, and erythrocyte sedimentation rates were collected. Clinical response and clinical remission were assessed using modified Mayo. Endoscopic evaluation was performed carried out using the Mayo Endoscopic Score and Ulcerative colitis endoscopic index of severity score. A total of 14 patients who received upadacitinib were included in the study period. All patients exhibited a clinical response to 45 mg upadacitinib initially. All patients completed the 8-week induction. The clinical remission rate was 28.6% after eight weeks. Two patients revealed endoscopic remission at 14.3%. The pathology improved in 50.0% of patients. The 8-week surgical resection rate was 7.1%, with the 16-week surgical resection rate being 14.3%. Adverse events included herpes simplex virus infection and increased thrombin time. The results of our study support the short-term effectiveness and safety of upadacitinib in acute severe ulcerative colitis, providing new choices for patients' treatment. However, more extended investigation needs to be performed on the long-term effectiveness and safety. [ABSTRACT FROM AUTHOR]

Excessive proinflammatory cytokine release induced by pyroptosis plays a vital role in intestinal mucosal inflammation in ulcerative colitis (UC). Several pyroptosis‐related factors are regulated by the centrosome. Pericentriolar material 1 (PCM1) is a primary component of centriolar satellites that is present as cytoplasmic granules around the centrosome. Our previous study revealed that PCM1 was highly expressed in UC patients, but the role of PCM1 in UC remains unknown. This study aimed to elucidate the role of PCM1 in the development of UC, especially the mechanism in pyroptosis process of UC. Clinical mucosal sample and dextran sulfate sodium (DSS)‐induced colitis mouse were used to reveal the association between PCM1 and intestinal inflammation. Intestinal epithelial cell‐specific PCM1‐knockout mice were constructed to determine the role of PCM1 in colitis. Finally, PCM1 RNA interference and overexpression assays in THP1 cells were employed to study the molecular mechanisms of PCM1 in inflammatory responses and pyroptosis. We found that PCM1 expression was upregulated in the colonic mucosa of UC patients and positively correlated with inflammatory indicators. PCM1 expression was elevated in DSS‐induced colitis mice and was reduced after methylprednisolone treatment. In the DSS colitis model, intestinal‐specific PCM1‐knockout mice exhibited milder intestinal inflammation and lower pyroptosis levels than wild‐type mice. In cell level, PCM1 exerted a proinflammatory effect by activating the NLRP3 inflammasome and triggering subsequent gasdermin D‐mediated pyroptosis to release IL‐1β and IL‐18. In conclusion, PCM1 mediates activation of the NLRP3 inflammasome and gasdermin D‐dependent pyroptosis, ultimately accelerating intestinal inflammation in UC. These findings revealed a previously unknown role of PCM1 in initiating intestinal mucosal inflammation and pyroptosis in UC, and this factor is expected to be a regulator in the complex inflammatory network of UC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tulisokibart is a tumor necrosis factor-like cytokine lA (TLlA) monoclonal antibody in development for the treatment of moderately to severely active ulcerative colitis. A genetic-based diagnostic test was designed to identify patients with ati increased likelihood of response. METHODS: We randomly assigned patients with glucocorticoid dependence or failure of conventional or advanced therapies for ulcerative colitis to receive intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10) or placebo. Cohort 1 included Gastroenterpatients regardless of status with respect to the test for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response. The primary analysis was performed in cohort 1; the primary end point was clinical remission at week 12. Patients with a positive test for likelihood of response from cohorts 1 and 2 were combined in prespecified analyses. RESULTS: In cohort 1, a total of 135 patients underwent randomization. A significantly higher percentage of patients who received tulisokibart had clinical remission than Gastroenterthose who received placebo (26% vs. 1%; difference, 25 percentage points; 95°/0 confidence interval [CI], 14 to 37; P<0.001). In cohort 2, a total of 43 patients underwent randomization. A total of 75 patients with a positive test for likelihood Wiof response underwent randomization across both cohorts. Among patients with Instia positive test for likelihood of response (cohorts 1 and 2 combined), clinical remission occurred in a higher percentage of patients who received tulisokibart than in those who received placebo (32% vs. 1196; difference, 21 percentage points; 95% CI, 2 to 38; P= 0.02). Among all the enrolled patients, the incidence of adverse events Anwas similar in the tulisokibart and placebo groups; most adverse events were mild to moderate in severity. CONCLUSIONS: In this short-term trial, tulisokibart was more effective than placebo in inducing clinical remission in patients with moderately to severely active ulcerative colitis. [ABSTRACT FROM AUTHOR]

Background: Qin-Yu-Qing-Chang decoction (QYQC), an herbal formula from China, is extensively employed to manage ulcerative colitis (UC) and exhibits potential benefits for colonic function. Nevertheless, the fundamental molecular mechanisms of QYQC remain largely uncharted. Methods: The primary constituents of QYQC were determined utilizing UHPLC-MS/MS analysis and the effectiveness of QYQC was assessed in a mouse model of colitis induced by dextran sulfate sodium. Evaluations of colon inflammatory responses and mucosal barrier function were thoroughly assessed. RNA sequencing, molecular docking, colonic energy metabolism, and 16S rRNA sequencing analysis were applied to uncover the complex mechanisms of QYQC in treating UC. Detect the signal transduction of the peroxisome proliferator-activated receptor-γ (PPAR-γ) both in the nucleus and cytoplasm. Furthermore, a PPAR-γ antagonist was strategically utilized to confirm the functional targets that QYQC exerts. Results: Utilizing UHPLC-MS/MS, the principal constituents of the nine traditional Chinese medicinal herbs comprising QYQC were systematically identified. QYQC treatment substantially ameliorated colitis in mice, as evidenced by the improvement in symptoms and the reduction in colonic pathological injuries. Besides, QYQC treatment mitigated the inflammatory response and improved mucosal barrier function. Furthermore, QYQC enhanced the mitochondria citrate cycle (TCA cycle) by triggering PPAR-γ signaling and increasing the proportion of PPAR-γ entering the nucleus. This prevented the unconstrained expansion of facultative anaerobes, particularly pathogenic Escherichia coli (E. coli, family Enterobacteriaceae) and thus improved colitis. Results of molecular docking indicated that the representative chemical components of QYQC including Baicalin, Paeoniflorin, Mollugin, and Imperatorin bound well with PPAR-γ. The impact of QYQC on colitis was diminished in the presence of a PPAR-γ antagonist. Conclusions: In summary, QYQC ameliorates UC by activating PPAR-γ signaling and increasing the proportion of PPAR-γ entering the nucleus, which enhances the energy metabolism of intestinal epithelial cells and thereby preventing the uncontrolled proliferation of facultative anaerobes. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) comprises Crohn's disease (CD) and ulcerative colitis (UC), both characterized by chronic intestinal inflammation and an elevated risk of colorectal cancer due to persistent inflammation. The Regenerating gene (Reg) family proteins exhibit properties that promote cell proliferation, inhibit apoptosis, reduce inflammation, combat microbial infections, and potentially modulate the immune system. There is increasing evidence of the potential function of the Reg family of proteins in the development of IBD and colorectal cancer, but the exact mechanism of action of the Reg family of proteins has not yet been fully clarified. In this paper, we reviewed the Reg protein family's involvement in the development of IBD by regulating intestinal microbes and immunity to maintain intestinal homeostasis. We also explored its possible regulatory mechanisms and signaling pathways in the progression and treatment of colorectal cancer, which is expected to serve as a target and a new biomarker for the treatment of IBD and colorectal cancer in the future. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion Ulcerative colitis (UC) affects over 3 million (1.3%) US adults, approximately 20% of whom will require surgery. Since it was first described in 1978, restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) has become the gold standard for patients requiring surgery, as well as for patients with familial adenomatous polyposis (FAP). In 1991 the laparoscopic approach to IPAA was introduced. The aim of this study was to evaluate the advances made in IPAA as minimally invasive surgery (MIS) has become more prevalent.The American College of Surgeons NSQIP database from 2005 to 2019 was used. Laparoscopic (MIS) and open cases of IPAA construction for UC or FAP were used. These patients were subdivided into three time point cohorts: early (2005–2009), middle (2010–2014) and recent (2015–2019). Univariable and multivariable analyses were performed to evaluate morbidity, mortality and hospital length of stay.A total of 6184 patients were analysed, and 2555 underwent MIS while 3629 underwent open surgery. After multivariable analysis, the MIS approach was associated with a lower risk of morbidity compared with open procedures [relative risk (RR) = 0.86, p < 0.0001, 95% CI 0.78–0.94], both in the early and recent periods [early period = RR = 0.66 (p < 0.0001), recent period RR = 0.78 (p = 0.0029)]. Superficial surgical site infection (SSI) was consistently lower in the MIS cohort across all three time periods. After multivariable analysis, the overall RR of superficial SSI in the MIS cohort was 0.41 (p < 0.0001) [early period RR = 0.35 (p < 0.0001), middle period RR = 0.55 (p = 0.0007), recent period RR = 0.31 (p < 0.0001)]. The RR of deep space SSI was decreased overall (RR = 0.58, p = 0.013, 95% CI 0.62–0.93), with the most significant effect occurring during the early period (RR = 0.30, p = 0.0260, 95% CI 0.105–0.868). Sepsis related to any infective aetiology was also decreased in the MIS cohort (RR = 0.76, p = 0.0093, 95% CI 0.62–0.93), especially in the recent time period (RR = 0.63, p = 0.0344, 95% CI 0.41–0.97). Furthermore, hospital length of stay was decreased in the MIS cohort (−0.287 days, p = 0.0170), with a greater difference occurring in the more recent cohort (−0.375 days, p = 0.0418).With increasing utilization of minimally invasive techniques in IPAA creation there have been significant decreases in the rates of morbidity including decreasing rates of superficial and deep space SSI, as well as decreased hospital length of stay. [ABSTRACT FROM AUTHOR]

Introduction: Crohn's disease (CD) is characterized by chronic inflammation and intestinal fibrosis leading to lifelong complications. However, the disease pathogenesis remains elusive, and the therapeutic options are limited. Here, we investigated the interaction between neutrophils and intestinal fibroblasts in the development of CD immunofibrosis, a disease mechanism predisposing to inflammatory and fibrotic complications. Methods: Peripheral neutrophils, enriched neutrophil extracellular traps (eNETs), serum, primary intestinal fibroblasts (PIFs) and intestinal biopsies from CD, ulcerative colitis (UC) patients, and healthy individuals (HI), were studied. Transcriptome analysis of neutrophils, multi-cytokine profiling and cell-based functional assays at mRNA/protein level were performed. Results: Compared to UC, PIFs from CD patients, independently to the presence of strictures, displayed a distinct pro-fibrotic phenotype characterized by negative Krüppellike Factor-2 (KLF2) and increased cellular communication network factor-2 (CCN2) expression leading to collagen production. In both UC and CD, PIFs-derived IL-8 acted as a culprit chemoattractant for neutrophils in the intestine, where CD neutrophils were accumulated close to fibrotic lesions. Functionally, only CD neutrophils via eNETs induced a CD-like phenotype in HI PIFs, suggesting their fibrotic plasticity. High IFNa in serum and IFα-responsive signature in peripheral neutrophils were observed in CD, distinguishing it from UC. Moreover, CD serum stimulated the release of fibrogenic eNETs from neutrophils in an IFNa-dependent manner, suggesting the priming role of IFNa in circulating neutrophils. Inhibition of eNETs or JAK signaling in neutrophils or PIFs prevented the neutrophil-mediated fibrotic effect on PIFs. Furthermore, both serum IFNa levels and mRNA levels of key IFN signaling components in neutrophils were wellcorrelated with CD severity. Conclusions: This study reveals the important role of the IFNa/neutrophil/fibroblast axis in CD immunofibrosis, suggesting candidate biomarkers and putative therapeutic targets. [ABSTRACT FROM AUTHOR]

Objectives: There is already substantial evidence indicating that neutrophil extracellular trap (NET) formation contributes to the inflammatory cascade in ulcerative colitis (UC). However, the precise regulatory mechanisms governing this process remain elusive. This study aimed to determine the role of NETrelated genes in UC and reveal possible mechanisms. Methods: Employing a two-sample MR methodology, we investigated the correlations between NET-associated genes (NRGs) and UC with summary data derived from a genome-wide association study (12,366 cases vs. 33,609 controls) and FinnGen (8,279 cases vs. 261,098 controls). The main analysis employed the inverse variance weighted method, supplemented by the MREgger method and weighted median method. Sensitivity analysis was conducted to rule out the interference of heterogeneity and pleiotropy among utilized instrument variables. The colocalization analysis was used to determine whether the identified NRGs and UC shared casual variants. Cross-tissue expression analysis was performed to characterize the expression patterns of target NRGs, while multi-gene correlation analysis and GSEA analysis were conducted to explore the mechanisms by which target NRGs promote UC and NET formation. Immunohistochemistry was used to validate the protein expression of target NRGs in the colon tissue of UC patients. Results: After the validation of two datasets, seven NRGs were associated with the risk of UC. The higher expression of ITGB2 was associated with increased UC risk, while the expression of CXCR1, CXCR2, IRAK4, MAPK3, SIGLEC14, and SLC22A4 were inversely associated with UC risk. Colocalization analysis supported the correlation between CXCR1/2 and UC risk. Expression analysis indicated that CXCR1/2 were down-regulated in peripheral blood, but upregulated in colon tissue. GSEA analysis and correlation analysis indicated that CXCR1/2 promoted UC and NET formation through neutrophil chemotaxis and PAD4-mediated pathways, separately. Immunohistochemical results confirmed the high expression of CXCR1/2 in colon tissues of UC patients. Conclusions: Our study identified CXCR1/2 as candidate targets in UC among all NRGs through multi-method argumentation, providing new insights of the regulation mechanisms of NET formation in the pathogenesis of UC. [ABSTRACT FROM AUTHOR]