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Radiation-induced morphea (RIM) is a rare complication of radiotherapy presenting as inflammatory fibrosis, most commonly reported in breast cancer patients. As underlying disease mechanisms are not well understood, targeted therapies are lacking. Since fibroblasts are the key mediators of all fibroproliferative diseases, this study aimed to characterize patient-derived fibroblasts to identify therapeutic targets. We studied primary human control and RIM-fibroblasts on a functional and molecular basis, analyzed peripheral blood and tissue samples and conducted, based on our findings, a treatment attempt in one patient. In RIM, we identified a distinct myofibroblast phenotype reflected by increased alpha-smooth-muscle-actin (αSMA) expression, reduced proliferation and migration rates, and overexpression of osteopontin (OPN). Our RNA sequencing identified aberrant Myc activation as a potential disease driver in RIM fibroblasts, similar to previous findings in systemic sclerosis. Treatment with the anti-inflammatory drug mesalazine reversed the myofibroblast phenotype by targeting Myc. Based on these findings, a patient with RIM was successfully treated with mesalazine, resulting in reduced inflammation and pain and tissue softening, while serum OPN was halved. The present study provides a comprehensive characterization of RIM fibroblasts, suggests a disease-driving role for Myc, demonstrates promising antifibrotic effects of mesalazine and proposes OPN as a biomarker for RIM. [ABSTRACT FROM AUTHOR]

Background: A subset of patients with irritable bowel syndrome (IBS) develop their symptoms after gastroenteritis, referred to as postinfectious IBS (PI‐IBS). PI‐IBS is associated with low‐grade intestinal inflammation. Previous studies have evaluated mesalamine, an anti‐inflammatory drug, in patients with IBS. We evaluated the efficacy of long‐acting mesalamine in patients with PI‐IBS. Methods: Sixty‐one patients who developed diarrhea‐predominant IBS (IBS‐D) after gastroenteritis were randomized to receive either 2.4 g of long‐acting mesalamine or placebo daily for 8‐weeks. The symptoms assessed were abdominal pain, bloating, stool frequency, stool consistency, severity of diarrhea and constipation, satisfaction with bowel habits, and IBS affecting or interfering with life. Quality‐of‐life (QOL) was assessed using the IBS‐QOL questionnaire. The prespecified primary outcome variable was the overall bowel symptom score (BSS) after 8‐weeks of treatment. Effect sizes were expressed as standardized mean differences (Cohen's d). Results: Fifty‐four patients completed the 8‐week treatment (n = 28 mesalamine, n = 26 placebo), 49 (91%) were male, and age range 23–71 years (mean ± SD 43 ± 13). Mesalamine demonstrated superior efficacy compared to placebo on the primary outcome variable, overall BSS (Cohen's d = 0.57, p = 0.042). Mesalamine was also superior for the secondary outcome of how much IBS affects your life in general (d = 0.72, p = 0.01). For the secondary outcomes of IBS symptoms, 7 of the 7 symptoms had trends of mesalamine superiority. For the secondary outcomes of IBS‐QOL subscales, 8 of 9 had trends of mesalamine superiority. Conclusion: In patients with PI‐IBS, long‐acting mesalamine demonstrated to be effective in reducing IBS symptoms and improving QOL. [ABSTRACT FROM AUTHOR]

Colonic drug delivery offers numerous pharmaceutical opportunities, including direct access to local therapeutic targets and drug bioavailability benefits arising from the colonic epithelium's reduced abundance of cytochrome P450 enzymes and particular efflux transporters. Current workflows for developing colonic drug delivery systems involve time-consuming, low throughput in vitro and in vivo screening methods, which hinder the identification of suitable enabling materials. Polysaccharides are useful materials for colonic targeting, as they can be utilised as dosage form coatings that are selectively digested by the colonic microbiota. However, polysaccharides are a heterogeneous family of molecules with varying suitability for this purpose. To address the need for high-throughput material selection tools for colonic drug delivery, we leveraged machine learning (ML) and publicly accessible experimental data to predict the release of the drug 5-aminosalicylic acid from polysaccharide-based coatings in simulated human, rat, and dog colonic environments. For the first time, Raman spectra alone were used to characterise polysaccharides for input as ML features. Models were validated on 8 unseen drug release profiles from new polysaccharide coatings, demonstrating the generalisability and reliability of the method. Further, model analysis facilitated an understanding of the chemical features that influence a polysaccharide's suitability for colonic drug delivery. This work represents a major step in employing spectral data for forecasting drug release from pharmaceutical formulations and marks a significant advancement in the field of colonic drug delivery. It offers a powerful tool for the efficient, sustainable, and successful development and pre-ranking of colon-targeted formulation coatings, paving the way for future more effective and targeted drug delivery strategies. [Display omitted] • A new Raman spectrum processing pipeline for effective Machine Learning. • Raman spectra of polysaccharide coatings can successfully predict 5-ASA release. • ML model is robust in human, rat and dog IBD-simulated colonic environments. • Model interpretation revealed coating molecular properties influencing 5-ASA release. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is defined by persistent inflammatory processes within the gastrointestinal tract of uncertain etiology. Current therapeutic approaches are limited in their ability to address oxidative stress, inflammation, barrier function restoration, and modulation of gut microbiota in a coordinated manner to maintain intestinal homeostasis. Results: This study involves the construction of a metal-phenolic nanozyme (Cur-Fe) through a ferric ion-mediated oxidative coupling of curcumin. Cur-Fe nanozyme exhibits superoxide dismutase (SOD)-like and •OH scavenging activities, demonstrating significant anti-inflammatory and anti-oxidant properties for maintaining intracellular redox balance in vitro. Drawing inspiration from Escherichia coli Nissle 1917 (EcN), a biomimetic Cur-Fe nanozyme (CF@EM) is subsequently developed by integrating Cur-Fe into the EcN membrane (EM) to improve the in vivo targeting ability and therapeutic effectiveness of the Cur-Fe nanozyme. When orally administered, CF@EM demonstrates a strong ability to colonize the inflamed colon and restore intestinal redox balance and barrier function in DSS-induced colitis models. Importantly, CF@EM influences the gut microbiome towards a beneficial state by enhancing bacterial diversity and shifting the compositional structure toward an anti-inflammatory phenotype. Furthermore, analysis of intestinal microbial metabolites supports the notion that the therapeutic efficacy of CF@EM is closely associated with bile acid metabolism. Conclusion: Inspired by gut microbes, we have successfully synthesized a biomimetic Cur-Fe nanozyme with the ability to inhibit inflammation and restore intestinal homeostasis. Collectively, without appreciable systemic toxicity, this work provides an unprecedented opportunity for targeted oral nanomedicine in the treatment of ulcerative colitis. [ABSTRACT FROM AUTHOR]

Introduction: Adherence to mesalamine therapy in ulcerative colitis is often inadequate. This affects long-term remission and to some extent the risk of colon cancer. Means for assessing non-adherent behavior are cumbersome, expensive, and/or time consuming. Unless multiple tools are used in association, a proportion of patients with volitional and non-volitional non-adherence is nonetheless undetected. The study was aimed at evaluating to which extent rephrasing a single question on adherence to mesalamine therapy may help identifying patients who are not compliant with medication prescription. Methods: One-hundred and seventy-four inflammatory bowel disease outpatients were asked in two consecutive visits, in random order, if they "regularly assumed the prescribed dose of mesalamine" (adherence-centered question—AQ) or "how often they skipped mesalamine pills" (non-adherence centered question—NQ). Answer concordance was evaluated in relation to clinical and demographic variables. Results: The concordance between AQ and NQ was low (K = 0.22). Lower compliance to therapy was admitted in 37.4% more patients following NQ than AQ. The reported adherence to AQ was invariably higher than that of NQ, irrespective of the variable taken into consideration. The likelihood of non-concordant answers was non-significantly higher in CD patients than in UC and in patients with shorter disease duration than in those with longstanding disease, but the logistic regression model did not identify individual variables responsible for the different answers. Conclusions: Being simple and not requiring additional time expense, centering the question on medication non-adherence identifies a large proportion of patients who would not admit non-adherence or underestimate the number of skipped doses of medication, when directly asked if they are compliant to therapy. [ABSTRACT FROM AUTHOR]

Background: Pyodermatitis-pyostomatitis vegetans (PPV) is a rare mucocutaneous disease characterized by multiple pustules and it is considered a marker for inflammatory bowel disease (IBD). The oral manifestations of this condition are referred to as pyostomatitis vegetans (PSV). Purpose: To investigate which features could help in establishing the diagnosis of PSV, with or without cutaneous lesions, based on information retrieved from all cases of PSV described in the literature. A case of PV from the authors was also included in the analysis. Methods: An electronic search was undertaken, last updated in August 2022. Inclusion criteria included publications reporting cases of PSV, with the diagnosis confirmed by the pathological examination of oral or skin lesions, and presence of IBD. Results/Conclusions: Sixty-two publications with 77 cases of PSV and an associated IBD were included. Features that are helpful in establishing the diagnosis of PSV are snail track appearance of oral lesions, an associated IBD (which is not always symptomatic), evidence of intraepithelial clefting on microscopic examination of oral lesions, and peripheral blood eosinophilia. A gold standard for the management of PSV does not exist and high-level evidence is limited. There is no established therapeutic protocol for PSV and management primarily consists of topical and/or systemic corticosteroids, antirheumatic drugs (sulfasalazine, mesalazine), monoclonal antibody (infliximab, adalimumab) immunosuppressives (azathioprine, methotrexate), antibiotics (dapsone), or a combination of these. The risk of recurrence of oral lesions is considerable when the medication dose is decreased or fully interrupted. [ABSTRACT FROM AUTHOR]

Sumaiah J Alarfaj,1 Mostafa M Bahaa,2 Thanaa A Elmasry,3 Eman I Elberri,4 Eman El-Khateeb,4 Amir O Hamouda,5 Muhammed M Salahuddin,5 Marwa Kamal,6 Abdel-Naser Abdel-Atty Gadallah,7 Nashwa Eltantawy,8 Mohamed Yasser,9– 11 Walaa A Negm,12 Manal A Hamouda,13 Amsha S Alsegiani,14 Sarah Alrubia,14 Mamdouh Eldesoqui,15 Mahmoud S Abdallah16,17 1Department of Pharmacy Practice, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; 2Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, Egypt; 3Pharmacology and Toxicology Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt; 4Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt; 5Department of Biochemistry and Pharmacology, Faculty of Pharmacy, Horus University, New Damietta, Egypt; 6Department of Clinical Pharmacy, Faculty of Pharmacy, Fayoum University, Fayoum, Egypt; 7Internal Medicine Department, Faculty of Medicine, Menofia University, Menofia, Egypt; 8Department of Pharmacy Practice, Faculty of Pharmacy and Drug Technology, Egyptian Chinese University, Cairo, Egypt; 9Department of Pharmaceutics, Faculty of Pharmacy, Port Said University, Port Said, Egypt; 10Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Horus University, New Damietta, Egypt; 11Department of Pharmaceutics, Faculty of Pharmacy, East Port Said National University, Port Said, Egypt; 12Pharmacognosy Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt; 13Department of Clinical Pharmacy, Faculty of Pharmacy, Menofia University, Menofia, Egypt; 14Pharmaceutical Chemistry Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 15Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia; 16Department of Clinical Pharmacy, Faculty of Pharmacy, University of Sadat City (USC), Sadat City, Menoufia, Egypt; 17Department of PharmD, Faculty of Pharmacy, Jadara University, Irbid, JordanCorrespondence: Mostafa M Bahaa, Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, 34517, Egypt, Tel +0201025538337, Email mbahaa@horus.edu.egBackground: Ulcerative colitis (UC) is an idiopathic chronic inflammation of colonic and rectal mucosa. The peroxisome proliferator-activated receptor α (PPARα) has been identified as having protective effects in UC.Aim: The study aimed to investigate the efficacy of fenofibrate, a PPARα agonist, in UC.Methods: A total of 70 patients with mild to moderate UC were allocated randomly and assigned to two groups (n = 35 each) from Gastroenterology Department, Faculty of Medicine, Menoufia University. The mesalamine group received a placebo along with 1 g of mesalamine three times daily, while the fenofibrate group received 1 g of mesalamine three times and fenofibrate 160 mg once daily. The study duration was for six months. A gastroenterologist assessed patients by non-invasive Partial Mayo Score (PMS) and the Inflammatory Bowel Disease Questionnaire (IBDQ) to evaluate clinical response and remission. The serum levels of silent information regulator 1 (SIRT1), NOD-like receptor protein 3 (NLRP3), and adenosine monophosphate activated protein kinase (AMPK), as well as fecal calprotectin levels were examined to determine the biological effect of fenofibrate.Results: After treatment, the fenofibrate group showed statistically significant reductions in PMS (p = 0.044) and improved digestive domain of IBDQ (p = 0.023). Additionally, there were significant decreases in serum NLRP3 (p = 0.041) and fecal calprotectin (p = 0.035), along with significant increases in SIRT1 (p = 0.002) and AMPK (p = 0.0003). The fenofibrate group also had higher response and remission rates compared to the mesalamine group.Conclusion: Fenofibrate may be a promising adjunct for improving clinical outcomes, quality of life, and modulating inflammation in mild to moderate patients with UC.Trial Registration Identifier: NCT05781698.Keywords: Ulcerative colitis, Fenofibrate, Mesalamine, NLRP3/AMPK, PPAR&#x03B1

Introduction: Adherence to mesalamine therapy in ulcerative colitis is often inadequate. This affects long-term remission and to some extent the risk of colon cancer. Means for assessing non-adherent behavior are cumbersome, expensive, and/or time consuming. Unless multiple tools are used in association, a proportion of patients with volitional and non-volitional non-adherence is nonetheless undetected. The study was aimed at evaluating to which extent rephrasing a single question on adherence to mesalamine therapy may help identifying patients who are not compliant with medication prescription. Methods: One-hundred and seventy-four inflammatory bowel disease outpatients were asked in two consecutive visits, in random order, if they “regularly assumed the prescribed dose of mesalamine” (adherence-centered question—AQ) or “how often they skipped mesalamine pills” (non-adherence centered question—NQ). Answer concordance was evaluated in relation to clinical and demographic variables. Results: The concordance between AQ and NQ was low (K = 0.22). Lower compliance to therapy was admitted in 37.4% more patients following NQ than AQ. The reported adherence to AQ was invariably higher than that of NQ, irrespective of the variable taken into consideration. The likelihood of non-concordant answers was non-significantly higher in CD patients than in UC and in patients with shorter disease duration than in those with longstanding disease, but the logistic regression model did not identify individual variables responsible for the different answers. Conclusions: Being simple and not requiring additional time expense, centering the question on medication non-adherence identifies a large proportion of patients who would not admit non-adherence or underestimate the number of skipped doses of medication, when directly asked if they are compliant to therapy.

The mechanism underlying intestinal fibrosis, the main complication of inflammatory bowel disease (IBD), is not yet fully understood, and there is no therapy to prevent or reverse fibrosis. We evaluated, in in vitro cellular models, the ability of different classes of drugs currently used in IBD to counteract two pivotal processes of intestinal fibrosis, the differentiation of intestinal fibroblasts to activated myofibroblasts using CCD-18Co cells, and the epithelial-to-mesenchymal transition (EMT) of intestinal epithelial cells using Caco-2 cells (IEC), both being processes induced by transforming growth factor-β1 (TGF-β1). The drugs tested included mesalamine, azathioprine, methotrexate, prednisone, methylprednisolone, budesonide, infliximab, and adalimumab. The expression of fibrosis and EMT markers (collagen-I, α-SMA, pSmad2/3, occludin) was assessed by Western blot analysis and by immunofluorescence. Of the drugs used, only prednisone, methylprednisolone, budesonide, and adalimumab were able to antagonize the pro-fibrotic effects induced by TGF-β1 on CCD-18Co cells, reducing the fibrosis marker expression. Methylprednisolone, budesonide, and adalimumab were also able to significantly counteract the TGF-β1-induced EMT process on Caco-2 IEC by increasing occludin and decreasing α-SMA expression. This is the first study that evaluates, using in vitro cellular models, the direct antifibrotic effects of drugs currently used in IBD, highlighting which drugs have potential antifibrotic effects. [ABSTRACT FROM AUTHOR]

Pentasa (mesalamine/MSLM) is a widely prescribed delayed‐release capsule formulation for the treatment of inflammatory bowel disease. During dissolution study of Pentasa through ultraviolet (UV) spectroscopy, an unusual end‐release of about 110% has been observed. Initial liquid chromatography‐UV (LC‐UV) analyses of these dissolution samples confirmed three prominent peaks other than MSLM with a significant area percentage. Further systematic investigation was carried out by incubating active pharmaceutical ingredient in dissolution media for a longer duration and at elevated temperature followed by analysis through an inverse gradient LC‐charged aerosol detector (CAD). LC–high‐resolution mass spectrometry (HRMS) and online hydrogen‐deuterium exchange (HDX) mass spectrometry were also employed to identify and characterize these artifact products. The area % of prominent artifacts in LC‐UV was found to be way significant when compared to the area % obtained through inverse LC‐CAD, as CAD quantifies the peaks independent of the UV wavelength of absorbance. Inverse LC‐CAD was suitable to determine the relative response factor, whereas LC‐HRMS/MS and online HDX‐MS supported the characterization of these artifacts. These artifacts were found to be trimers, tetramers of MSLM formed due to polymerization, imparting additional pi‐bonds resulting in high UV absorptivity. These techniques when used in combinations serve complimentary to each other during such investigations. [ABSTRACT FROM AUTHOR]

Introduction: Although there are well-defined guidelines for the management of mild-to-moderate ulcerative colitis (UC), there are still unmet needs. For this reason, we conducted an international expert consensus to standardize the management of patients with mild-to-moderate UC and provide practical guidance to clinicians. Areas covered: Based on Delphi methodology, 15 statements were approved after two rounds of voting, addressing several aspects of disease management from sequencing to treatment duration, from monitoring to optimization techniques and safety profile. Expert opinion: Growing knowledge of mild-to-moderate UC has led to the development of new ambitious outcomes such as histological remission and disease clearance. Furthermore, noninvasive tools for patient monitoring such as fecal calprotectin and intestinal ultrasound are now available. Their implementation in clinical practice will allow clinicians to tightly monitor disease activity and promptly adapt treatment, avoiding complications and disease progression and targeting better disease control. [ABSTRACT FROM AUTHOR]

Background: Iran has been one of the most affected countries in the world by COVID-19. The aim of our study was to determine the outcome of COVID-19 in patients with inflammatory bowel disease (IBD). Furthermore, we analyzed the outcome of SARS-CoV-2 infection in patients with IBD treated with immunosuppressant. Materials and Methods: This is a cross-sectional, observational study. This study included all patients with IBD, regularly followed up in our IBD Clinic at a tertiary medical center from February 5th, 2020 to August 5th, 2022. We identified those patients with confirmed SARS-CoV-2 infection either by PCR test or chest computed tomography (CT) imaging. Results: A total of 401 patients were recruited (n=346 [86.28%] with ulcerative colitis, n=53 [13.22%] with Crohn’s disease, and 2 [0.5%] with indeterminate colitis). Of these patients, 273 (68.08%) developed no symptoms or signs during the follow-up period,128 patients developed symptoms similar to COVID-19, and 76 (18.9%) were diagnosed as confirmed COVID-19 cases. Men comprised 60.5% of the confirmed COVID-19 groups, which shows that men were statistically more likely to have symptoms of COVID-19 during the follow-up period (P=0.04). No significant differences were observed among confirmed and non-COVID-19 cases in terms of concomitant medications: steroids (P=0.6), thiopurines (P=0.23), anti-TNF (P=0.23), and aminosalicylate (P=0.61). Three patients required hospitalization, but there were no admissions to the intensive care unit or deaths related to COVID-19. Conclusion: The risk of COVID-19-related adverse outcomes and death in patients with IBD is low. Also, patients with IBD under immunosuppressive treatment are not at an increased risk of COVID-19. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic inflammatory bowel disease mainly affecting the colon and remains a challenging disease to manage clinically with its relapsing-remitting course. Traditional treatments for this disease showed some drawbacks, including systemic toxicity and ineffective targeting of the affected colon areas. This article introduces a unique treatment method that uses mesalazine (MSZ)-loaded TPP/Chitosan nanoparticles (MSZNP)-embedded into bovine serum albumin (BSA) hydrogels (MSZNPH) for targeted intrarectal medication delivery. Additionally, conventional MSZ was integrated into BSA hydrogel (MSZH), and then, MSZH, MSZNP, and MSZNPH were characterized and compared with an emphasis on encapsulation efficiency, drug release profile, and hydrogel swelling behavior. Our findings show that MSZNPH composite technology may improve targeted administration and prolonged release of MSZ, indicating a promising new route for UC therapy with the potential to improve patient adherence and outcomes. [ABSTRACT FROM AUTHOR]

Background: This study aimed to develop an efficient drug delivery system targeting the colon to treat inflammatory conditions using mesalamine. The approach involved formulating microsponges with Eudragit polymers, focusing on assessing the in vitro drug release patterns. Materials and Methods: The quasi-emulsion solvent diffusion method was employed using various Eudragit polymers (S100, L100, RS100 and RL100). Critical parameters, such as entrapment efficiency, particle size and drug release, were systematically examined. Different kinetic models have been used to understand the mechanism of drug release. Results and Discussion: The developed microsponges met the desired entrapment efficiency and particle size standards. Drug release from these formulations exhibited a diffusion-based pattern aligned with a zero-order kinetic model. Initial 1-2 hr showed minimal drug release (2-1%), whereas a significant release (92-95%) occurred within 24 hr for formulations F1 and F2. This release behaviour suggests the potential of sustained and pH-dependent drug delivery applications. Conclusion: This study contributes to the field by successfully designing a colon-targeted drug delivery system for mesalamines. Using Eudragit polymers and incorporating microsponges showed the potential for sustained drug release, emphasizing their applicability for treating inflammatory colon conditions. This study provides a foundation for future drug-delivery systems targeting specific gastrointestinal regions. [ABSTRACT FROM AUTHOR]

Objective: To clarify the potential mechanism of Banxia Xiexin Decoction (BXD) on colorectal cancer (CRC) from the perspective of metabolomics. Methods: Forty male C57BL/6 mice were randomly divided into normal control (NC), azoxymethane/dextran sulfate sodium (AOM/DSS) model, low-dose BXD (L-BXD), high-dose BXD (H-BXD) and mesalamine (MS) groups according to a random number table, 8 mice in each group. Colorectal cancer model was induced by AOM/DSS. BXD was administered daily at doses of 3.915 (L-BXD) and 15.66 g/kg (H-BXD) by gavage for consecutive 21 days, and 100 mg/kg MS was used as positive control. Following the entire modeling cycle, colon length of mice was measured and quantity of colorectal tumors were counted. The spleen and thymus index were determined by calculating the spleen/thymus weight to body weight. Inflammatory cytokine and changes of serum metabolites were analyzed by enzyme-linked immunosorbent assay kits and ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS), respectively. Results: Notably, BXD supplementation protected against weight loss, mitigated tumor formation, and diminished histologic damage in mice treated with AOM/DSS (P<0.05 or P<0.01). Moreover, BXD suppressed expression of serum inflammatory enzymes, and improved the spleen and thymus index (P<0.05). Compared with the normal group, 102 kinds of differential metabolites were screened in the AOM/DSS group, including 48 potential biomarkers, involving 18 main metabolic pathways. Totally 18 potential biomarkers related to CRC were identified, and the anti-CRC mechanism of BXD was closely related to D-glutamine and D-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, nitrogen metabolism and so on. Conclusion: BXD exerts partial protective effects on AOM/DSS-induced CRC by reducing inflammation, protecting organism immunity ability, and regulating amino acid metabolism. [ABSTRACT FROM AUTHOR]

Mesalazine is an established and recommended first-line treatment for mild-tomoderate ulcerative colitis (UC). For patients with moderately active UC, the choice to use mesalazine or to initiate treatment with an oral corticosteroid or anti-tumor necrosis factor (TNF) agent is not clearly informed from current guidelines. The use of mesalazine is supported by robust clinical evidence supporting its efficacy at inducing remission in patients with moderately active disease. A key advantage of mesalazine is its tolerability profile being similar to that of placebo, which contrasts with that of the corticosteroids and advanced therapies, where there is the potential for significant toxicities. Mesalazine also has cost advantages over anti-TNFs and other advanced therapies. Evidence supports the consideration of all patients with moderately active UC for first-line mesalazine therapy at an optimized dose of ≥4g/d (± 1g/d rectal). Patients responding to treatment within 2 weeks should continue at ≥4g/d for at least 6 months before a dose reduction is considered, since this then alters the pattern of disease. [ABSTRACT FROM AUTHOR]

Purpose: Current pharmacological treatments for Ulcerative Colitis (UC) have limitations. Therefore, it is important to elucidate any available alternative or complementary treatment, and Chinese herbal medicine shows the potential for such treatment. As a traditional Chinese herbal medicine, Danshenrelated preparations have been reported to be beneficial for UC by improving coagulation function and inhibiting inflammatory responses. In spite of this, the credibility and safety of this practice are incomplete. Therefore, in order to investigate whether Danshen preparation (DSP) is effective and safe in the treatment of UC, we conducted a systematic review and meta-analysis. Methods: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database and CQVIP Database were searched for this review. The main observation indexes were the effect of DSP combined with mesalazine or DSP on the effective rate, platelet count (PLT), mean platelet volume (MPV) and C-reactive protein (CRP) of UC. The Cochrane risk of bias tool was used to assess the risk of bias. The selected studies were evaluated for quality and data processing using RevMan5.4 and Stata17.0 software. Results: A total of 37 studies were included. Among them, 26 clinical trials with 2426 patients were included and 11 animal experimental studies involving 208 animals were included. Meta-analysis results showed that compared with mesalazine alone, combined use of DSP can clearly improve the clinical effective rate (RR 0.86%, 95% CI:0.83-0.88, p < 0.00001) of UC. Furthermore it improved blood coagulation function by decreasing serum PLT and increasing MPV levels, and controlled inflammatory responses by reducing serum CRP, TNF-α, IL-6, and IL-8 levels in patients. Conclusion: Combining DSP with mesalazine for UC can enhance clinical efficacy. However, caution should be exercised in interpreting the results of this review due to its flaws, such as allocation concealment and uncertainty resulting from the blinding of the study. [ABSTRACT FROM AUTHOR]

Treatment with immune checkpoint inhibitors is effective in various cancers, but may be associated with immune-mediated side effects in other organs. Among the more common ones is gastrointestinal tract involvement, especially colitis. In most patients, colitis is mild or responds to corticosteroid treatment. A smaller proportion of patients, more often those treated with cytotoxic T lymphocyte antigen-4 inhibitors, may have a more severe course of colitis, even life-threatening complications. In these patients, prompt action, timely diagnosis with endoscopic evaluation and early treatment with high-dose corticosteroids and, if ineffective, rescue therapy with biologic agents such as infliximab and vedolizumab are needed. We present three cases from our clinical practice, data on incidence and clinical presentation, current recommendations regarding diagnostic approach and treatment of immune checkpoint inhibitors induced colitis. [ABSTRACT FROM AUTHOR]

Background: Extraintestinal manifestations (EIMs) of inflammatory bowel diseases (IBDs) are a common and debilitating feature of disease, occurring in up to 40% of patients with IBD. Despite the huge therapeutic progress of the last decade, one must not forget about the side effects that currently available medications might have and the challenges to both patient and physician. Case presentation: We present the case of a 33-year-old woman, that initially was admitted for diffuse abdominal pain, nausea and bloating. After careful investigation she was diagnosed with a drug induced acute pancreatitis, caused by sulfamethoxazole/trimethoprim taken for UTI. Further investigations established a diagnosis of ulcerative colitis. Initial treatment with mesalamine resulted in another acute pancreatitis event that required hospitalization. An anti-TNF therapy with infliximab was started with initial clinical remission but then she developed another adverse reaction, this time paradoxical psoriasis, while having an IBD flare. So, this begged the question, how do we treat a patient that had an adverse reaction to every prior treatment? Conclusion: Developing newer and newer therapies will bring also different possible adverse events that should be carefully diagnosed and managed.

AbstractObjective: This study is aimed at investigating the impact of mesalamine combined with Live combined Bifidobacterium, Lactobacillus and Enterococcus capsules on intestinal mucosa barrier function and intestinal microbiota in mildly active Crohn’s disease patients.Methods: Ninety-six Crohn’s disease patients in mild activity period were randomized into the control group (treated with mesalamine) and the observation group (treated with mesalamine combined with Live combined Bifidobacterium, Lactobacillus and Enterococcus capsules) (n = 48). After 4 wk of treatment, the patients were evaluated for their clinical efficacy. Intestinal microbiota counts, serum inflammatory factors, T lymphocyte subsets, and mucosal barrier function indicators in both groups were assessed.Results: After 4 wk of treatment, the total clinical effective rate of the observation group was higher than that of the control group. The number of Lactobacillus acidophilus (L. acidophilus) and Bifidobacterium Longum (B. longum) in the intestinal tract, serum IL-10 levels, and peripheral blood CD4+ and CD4+/CD8+ levels were higher, and the number of Bacteroides vulgatus (B. vulgatus), the levels of TNF-α, IL-6, CRP, CD8+, ET, D-lactate, DAO, and urine L/M ratio were lower in the observation group in comparison to those in the control group (all p

Traditional Chinese medicine (TCM) serves as a significant adjunct to chemical treatment for chronic diseases. For instance, the administration of Baitouweng decoction (BTWD) has proven effective in the treatment of ulcerative colitis. However, the limited understanding of its pharmacokinetics (PK) has impeded its widespread use. Chinese Bama miniature pigs possess anatomical and physiological similarities to the human body, making them a valuable model for investigating PK properties. Consequently, the identification of PK properties in Bama miniature pigs can provide valuable insights for guiding the clinical application of BTWD in humans. To facilitate this research, a rapid and sensitive UPLC-MS/MS method has been developed for the simultaneous quantification of eleven active ingredients of BTWD in plasma. Chromatographic separation was conducted using an Acquity UPLC HSS T3 C18 column and a gradient mobile phase comprising acetonitrile and water (containing 0.1% acetic acid). The methodology was validated in accordance with the FDA Bioanalytical Method Validation Guidance for Industry. The lower limit of quantitation fell within the range of 0.60–2.01 ng/mL. Pharmacokinetic studies indicated that coptisine chloride, berberine, columbamine, phellodendrine, and obacunone exhibited low C max , while fraxetin, esculin, fraxin, and pulchinenoside B 4 were rapidly absorbed and eliminated from the plasma. These findings have implications for the development of effective components in BTWD and the adjustment of clinical dosage regimens. [ABSTRACT FROM AUTHOR]

Background: Seroprevalence of Epstein-Barr virus (EBV) in patients with inflammatory bowel disease (IBD) is variable based on geographic distribution. There are no published data on the seroprevalence of EBV in patients with IBD in Saudi Arabia. This study aims to assess the seroprevalence of EBV in patients with IBD in a tertiary center in Saudi Arabia. Methods: This is a retrospective chart review of patients ≥14 years of age with a confirmed diagnosis of IBD and known EBV status at our institution from January 1, 2018, to January 1, 2023. The primary outcome was the seroprevalence of EBV in IBD. Secondary outcomes included factors associated with EBV seropositivity and rates of EBV seroconversion in originally negative patients. Results: A total of 150 patients were included (74.7% with Crohn's disease, median age 28 years [interquartile range 21-36.3]). EBV non-exposure was noted in 16.8% (n = 25). The mean age was significantly lower in the EBV-naïve group at 26 ± 8.5 years compared to the EBV-exposed group at 31.2 ± 12.9 years (P = 0.02). Seroprevalence of EBV was highest in patients >40 years of age (92.9%) and lowest in patients 14-25 years of age (78.2%). The rate of seroconversion in EBV-naïve patients was 16.7% after a mean follow-up time of 47.9 ± 46.3 months. Conclusion: In our cohort of IBD patients, 16.8% were naïve to EBV, and young age was a significant predictor of EBV non-exposure. Our data supports the practice of assessing EBV before initiating thiopurine therapy since EBV seroprevalence is not universal in our population. [ABSTRACT FROM AUTHOR]

Successful treatment of ulcerative colitis (UC) is highly dependent on several parameters, including dosing regimen and the ability to deliver drugs to the disease site. In this study two strategies for delivering mesalazine (5-aminosalicylic acid, 5-ASA) to the colon were compared in an advanced in vitro model of the human gastrointestinal (GI) tract, the SHIME® system. Herein, a prodrug strategy employing bacteria-mediated drug release (sulfasalazine, Azulfidine®) was evaluated alongside a formulation strategy that utilised pH and bacteria-mediated release (5-ASA, Octasa® 1600 mg). SHIME® experiments were performed simulating both the GI physiology and colonic microbiota under healthy and inflammatory bowel disease (IBD) conditions, to study the impact of the disease state and ileal pH variability on colonic 5-ASA delivery. In addition, the effects of the products on the colonic microbiome were investigated by monitoring bacterial growth and metabolites. Results demonstrated that both the prodrug and formulation approaches resulted in a similar percentage of 5-ASA recovery under healthy conditions. On the contrary, during experiments simulating the GI physiology and microbiome of IBD patients (the target population) the formulation strategy resulted in a higher proportion of 5-ASA delivery to the colonic region as compared to the prodrug approach (P < 0.0001). Interestingly, the two products had distinct effects on the synthesis of key bacterial metabolites, such as lactate and short chain fatty acids, which varied according to disease state and ileal pH variability. Further, both 5-ASA and sulfasalazine significantly reduced the growth of the faecal microbiota sourced from six healthy humans. The findings support that the approach selected for colonic drug delivery could significantly influence the effectiveness of UC treatment, and highlight that drugs licensed for UC may differentially impact the growth and functioning of the colonic microbiota. [Display omitted] • The semi-dynamic SHIME® system modelled the GI tract in the healthy and IBD states. • Prodrug and formulation strategies for colonic 5-ASA delivery were compared. • The formulation strategy delivered a higher proportion of 5-ASA to the IBD colon. • The two IBD medications had distinct effects on gut microbiome metabolism. • 5-ASA and sulfasalazine reduced the growth of healthy gut microbiota. [ABSTRACT FROM AUTHOR]

Neutrophil extracellular traps (NETs) are induced in the innate immune response against infectious agents and are also implicated in the pathogenesis of various cancers and autoimmune diseases. Peptidylarginine deiminase 4 (PAD4), an enzyme that converts arginine to citrulline, is also involved in NET formation. In this study, we investigated the pathogenic effect of PAD4 on NETs in inflammatory bowel disease using a trinitrobenzene sulfonic acid (TNBS)-induced murine colitis model. PAD4-deficient (PAD4KO) mice were generated by CRISPR-Cas9-mediated genomic editing. NETs were triggered in peritoneal neutrophils obtained from wild-type mice by A23187 (a calcium ionophore), but these responses were completely abolished in the PAD4KO mice. Experimental colitis was induced in wild-type and PAD4KO mice via an intrarectal injection of TNBS. TNBS injection resulted in body weight loss, extensive colonic erosion, and ulceration in wildtype mice. However, these responses were significantly attenuated following the administration of Cl-amidine (an inhibitor of pan-PADs) and DNase I (an inhibitor of NET formation), in combination with PAD4KO in mice. TNBS-induced increases in myeloperoxidase activity, inflammatory cytokine expression, and NET formation in the colon were significantly reduced following the administration of Cl-amidine, DNase I injection, and PAD4KO. These findings suggest that NET formation contributes to the pathogenesis of TNBS-induced colitis via PAD4. Thus, PAD4 is a promising target for the treatment of inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Introduction: P. candolleana Wight et Arn. Is a traditional Chinese herbal medicine used by the Gelao nationality in southwest China, has been historically applied to treat various gastrointestinal disorders. Despite its traditional usage, scientific evidence elucidating its efficacy and mechanisms in treating ulcerative colitis (UC) remains sparse. This study aimed to determine the quality and chemical composition of Pimpinella candolleana and to identify its potential therapeutic targets and mechanisms in acetic acid-induced ulcerative colitis (UC) rats through integrated approaches. Methods: Morphological and microscopic characteristics, thin layer chromatography (TLC) identification, and quantitative analysis of P. candolleana were performed. UPLC-Q-TOF-MS, network pharmacology, and molecular docking were used to identify its chemical composition and predict its related targets in UC. Furthermore, a rat model was established to evaluate the therapeutic effect and potential mechanism of P. candolleana on UC. Results: Microscopic identification revealed irregular and radial arrangement of the xylem in P. candolleana, with a light green cross-section and large medullary cells. UPLC-Q-TOF-MS analysis detected and analyzed 570 metabolites, including flavonoids, coumarins, and terpenoids. Network pharmacology identified 12 effective components and 176 target genes, with 96 common targets for P. candolleana-UC, including quercetin, luteolin, and nobiletin as key anti-inflammatory components. GO and KEGG revealed the potential involvement of their targets in RELA, JUN, TNF, IKBKB, PTGS2, and CHUK, with action pathways such as PI3K-Akt, TNF, IL-17, and apoptosis. Molecular docking demonstrated strong affinity and binding between these key components (quercetin, luteolin, and nobiletin) and the key targets of the pathway, including JUN and TNF. Treatment with P. candolleana improved body weight loss, the disease activity index, and colonic histological damage in UC rats. Pimpinella candolleana also modulated the levels of IL-2 and IL-6 in UC rats, reduced the expression of pro-inflammatory cytokines such as IL-6, MAPK8, TNF-a, CHUK, and IKBKB mRNA, and decreased the expression of TNF, IKBKB, JUN, and CHUK proteins in the colon of UC rats, thereby reducing inflammation and alleviating UC symptoms. Conclusion: P. candolleana exerts its protective effect on UC by reducing the expression of proinflammatory cytokines and inhibiting inflammation, providing scientific evidence for its traditional use in treating gastrointestinal diseases. This study highlights the potential of P. candolleana as a natural therapeutic agent for UC and contributes to the development of novel medicines for UC treatment. [ABSTRACT FROM AUTHOR]