Phenotype-Led Identification of IL-10 Upregulators in Human CD4 T-cells and Elucidation of Their Pharmacology as Highly Selective CDK8/CDK19 Inhibitors.

Therapeutics promoting the endogenous production of IL-10 have the potential to restore homeostasis in inflammatory disorders such as inflammatory bowel disease (IBD). Here we describe the identification of a series of IL-10 upregulators based on a pyrimidyl-piperidine scaffold through a high throughput phenotypic CD4 T-cell multiplex assay. optimization of the initial hit yielded a lead with good potency and an clearance profile, compound 3-7, which additionally demonstrated efficacy in a murine endotoxin challenge PK-PD mechanistic model.

Developing and evaluating a gamified self-management application for inflammatory bowel disease using the ADDIE model and Sukr framework.

Background: The prevalence and chronic nature of Inflammatory Bowel Diseases (IBD) is a significant global concern. As the essential part of treatments approach, patient adherence to treatment protocols and self-management practices are crucial to = IBD management. Healthcare initiatives focused on chronic conditions are strongly needed to consider various aspects of gamification and how it can positively affect self-management.

Genomic characterization of Escherichia coli with a polyketide synthase (pks) island isolated from ulcerative colitis patients.

The E. coli strains harboring the polyketide synthase (pks) island encode the genotoxin colibactin, a secondary metabolite reported to have severe implications for human health and for the progression of colorectal cancer. The present study involves whole-genome-wide comparison and phylogenetic analysis of pks harboring E.

Host metabolism balances microbial regulation of bile acid signalling.

Metabolites derived from the intestinal microbiota, including bile acids (BA), extensively modulate vertebrate physiology, including development, metabolism, immune responses and cognitive function. However, to what extent host responses balance the physiological effects of microbiota-derived metabolites remains unclear. Here, using untargeted metabolomics of mouse tissues, we identified a family of BA-methylcysteamine (BA-MCY) conjugates that are abundant in the intestine and dependent on vanin 1 (VNN1), a pantetheinase highly expressed in intestinal tissues.

Association between allergic diseases and mucosal healing in ulcerative colitis.

Allergic diseases and ulcerative colitis (UC) share pathophysiological similarities. This study aimed to investigate the unclear association between allergic diseases and mucosal healing (MH), an important factor in the prognosis of UC. We studied 289 Japanese patients with UC.

Erythema nodosum, malignant melanoma and non-melanoma skin cancer in relation to inflammatory bowel disease: a Mendelian randomization study.

Inflammatory bowel disease (IBD) is a multisystem condition that could affect the cutaneous systems, namely cutaneous extraintestinal manifestations (EIMs). It has been suggested that IBD is associated with erythema nodosum (EN), malignant melanoma (MM) and non-melanoma skin cancer (NMSC). However, the potential causal relationship between IBD and the mentioned above cutaneous EIMs is still unclear.

Addressing Factors that Impact Sexual Well-Being and Intimacy in IBD Patients.

Purpose Of Review: This review details the pathophysiologic mechanisms from medical, surgical to psychosocial factors that illustrate how and why sexual health and intimacy are impacted in IBD.

Recent Findings: Recent clinical surveys of practicing gastroenterologists document that clinicians should routinely address sexual health when addressing patient reported outcomes but very few actually make direct inquiry or suggest management into this important aspect of human life. Example 'patter' are suggested to clinicians to demonstrate how to introduce the subject of sexual intimacy and well-being and engender patient trust on this sensitive topic.

Angelica gigas Nakai (Korean Dang-gui) Root Alcoholic Extracts in Health Promotion and Disease Therapy - active Phytochemicals and In Vivo Molecular Targets.

Angelica gigas Nakai (AGN) root is a medicinal herbal widely used in traditional medicine in Korea. AGN root ethanolic extracts have been marketed as dietary supplements in the United States for memory health and pain management. We have recently reviewed the pharmacokinetics (PK) and first-pass hepatic metabolism of ingested AGN supplements in humans for the signature pyranocoumarins decursin (D, C 1x), decursinol angelate (DA, C ~ 10x) and their common botanical precursor and hepatic metabolite decursinol (DOH, C ~ 1000x).

Wound Healing After Vaginal Delivery, Episiotomy, and Cesarean Section Delivery Among Women With IBD: Results From the PIANO Registry.

Background: Women with inflammatory bowel disease (IBD) face complexities of disease management during pregnancy and childbirth. Apprehension regarding vaginal delivery in pregnant individuals with IBD persists due to concern for perianal disease and perineal trauma. The incidence of poor wound healing after obstetric anal sphincter injury is approximately 4% in the general population.

Hepatobiliary manifestations of inflammatory bowel disease in Saudi Arabia: A retrospective analysis.

Objectives: To evaluate the features and frequency of hepatobiliary diseases in individuals with Inflammatory bowel disease (IBD).

Methods: This retrospective study included all IBD patients at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. The primary focus was on the prevalence of hepatobiliary diseases, such as primary sclerosing cholangitis (PSC), non-alcoholic fatty liver disease (NAFLD), autoimmune hepatitis (AIH), and others.

Eurotium-Cristatum fermented black tea alleviates ulcerative colitis through the PPARγ-NF-κB signaling axis.

Ulcerative colitis (UC) is a chronic inflammatory bowel condition that significantly impairs patient quality of life and remains incurable. Effective dietary management is crucial for both prevention and treatment. This study investigates the effects and mechanisms of Eurotium cristatum-fermented black tea (FBT) in a dextran sulfate sodium (DSS)-induced UC mouse model using transcriptome sequencing, immunofluorescence, and flow cytometry.

Tailored strategies based on polysaccharide structural and functional properties for nutrients delivery in inflammatory bowel disease.

Many food nutrients suffer from a series of limitations such as poor water solubility, low stability and inadequate bioavailability. These challenges can be effectively improved by food-based delivery systems (FDSs). FDSs are a series of functional carriers developed based on food-borne macromolecules.

Cardiovascular events observed among patients in the etrasimod clinical programme: an integrated safety analysis of patients with moderately to severely active ulcerative colitis.

Objective: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). S1P receptor expression on cardiac cells is involved in cardiac conduction. We report cardiovascular treatment-emergent adverse events (TEAEs) associated with S1P receptor modulators and other cardiovascular events in the etrasimod UC clinical programme.

Effect of a single rectal fecal microbiota transplantation on clinical severity and fecal microbial communities in dogs with chronic inflammatory enteropathy.

Background: Fecal microbiota transplantation (FMT) has been advocated as a treatment for chronic enteropathy (CE) in dogs. However, so far only short-term clinical effects have been reported whereas the effect on the microbiota remains unexplored.

Hypothesis/objectives: Assess if a single FMT enema can lead to clinical improvement in dogs with CE when accompanied by presumed favorable microbiota changes.

Vitamin D receptor regulates methyltransferase like 14 to mitigate colitis-associated colorectal cancer.

Colitis-associated colorectal cancer (CAC), a serious complication of ulcerative colitis (UC), is associated with a poor prognosis. The vitamin D receptor (VDR) is recognized for its protective role in UC and CAC through the maintenance of intestinal barrier integrity and the regulation of inflammation. This study demonstrates a significant reduction in mA-related genes, particularly methyltransferase like 14 (METTL14), in UC and CAC patients and identifies an association between METTL14 and VDR.

Is stapled Kono-S anastomosis a protective factor against postoperative endoscopic recurrence in Crohn's disease? a single-center, retrospective cohort study.

Background: Hand-sewn Kono-S anastomosis is safe and associated with a reduction in post-operative recurrence (POR) in Crohn's disease (CD). The study aims to investigate the advantages of stapled Kono-S in Crohn's patients with intestinal anastomosis.

Methods: Crohn's patients undergoing intestinal anastomosis were reviewed via a prospectively maintained database.

Diagnosing Crohn's Disease in Presumed Cryptoglandular Perianal Fistulas: An Expert Delphi Consensus on Early Identification of Patients at Risk of Crohn's Disease in Perianal Fistulas (PREFAB).

Background: The aim of this Delphi study was to reach consensus on a new clinical decision tool to help identify or exclude Crohn's disease (CD) in patients with perianal fistula(s) (PAF).

Methods: A panel of international experts in the field of proctology/Inflammatory Bowel Disease (IBD) were invited to participate. In the first round (electronic survey), participants were asked to anonymously provide their opinion probing 1) the relevance and use of clinical characteristics suggestive of underlying CD, 2) the use of faecal calprotectin (FCP) for screening for CD and 3) on the diagnostic work-up for CD in PAF patients with raised clinical suspicion.

Advances in bio-polymer coatings for probiotic microencapsulation: chitosan and beyond for enhanced stability and controlled release.

This review paper analyzes recent advancements in bio-polymer coatings for probiotic microencapsulation, with a particular emphasis on chitosan and its synergistic combinations with other materials. Probiotic microencapsulation is essential for protecting probiotics from environmental stresses, enhancing their stability, and ensuring effective delivery to the gut. The review begins with an overview of probiotic microencapsulation, highlighting its significance in safeguarding probiotics through processing, storage, and gastrointestinal transit.

Creeping fat and gut microbiota in Crohn's disease.

In this article, we explored the role of adipose tissue, especially mesenteric adipose tissue and creeping fat, and its association with the gut microbiota in the pathophysiology and progression of Crohn's disease (CD). CD is a form of inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract, influenced by genetic predisposition, gut microbiota dysbiosis, and environmental factors. Gut microbiota plays a crucial role in modulating immune response and intestinal inflammation and is associated with the onset and progression of CD.

Hepatobiliary and pancreatic manifestations in inflammatory bowel disease: an umbrella review of meta-analyses.

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), can affect the hepatobiliary system and pancreas, substantially impacting the life quality of patients.

Objectives: To evaluate the quality of evidence and comprehensively assess the validity of associations of IBD with hepatobiliary and pancreatic diseases.

Design: We performed an umbrella review of existing meta-analyses in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) recommendations.

A Standardized Approach to Transition Improves Care of Young Adults with Inflammatory Bowel Disease.

Introduction: Young adults with inflammatory bowel disease (IBD) are at the risk of poor outcomes when transferring to adult providers. We aimed to increase the percentage of patients with 14-17 years of age undergoing the transition of care and the percentage of patients 18-21 years of age initiating the transfer of care to 50% for 12 months. Our goal was also to improve patient satisfaction with the transfer process.

Alterations in Ileal Secretory Cells of The DSS-Induced Colitis Model Mice.

Inflammatory bowel disease is triggered by abnormalities in epithelial barrier function and immunological responses, although its pathogenesis is poorly understood. The dextran sodium sulphate (DSS)-induced colitis model has been used to examine inflammation in the colon. Damage to mucosa primality occurs in the large intestine and scarcely in the small intestine.

Drug repositioning of mesalamine via supramolecular nanoassembly for the treatment of drug-induced acute liver failure.

Acute liver failure (ALF) is characterized by rapid hepatic dysfunction, primarily caused by drug-induced hepatotoxicity. Due to the lack of satisfactory treatment options, ALF remains a fatal clinical disease, representing a grand challenge in global health. For the drug repositioning to ALF of mesalamine, which is clinically approved for the treatment of inflammatory bowel disease (IBD), we propose a supramolecular prodrug nanoassembly (SPNs).

Leaky Gut Syndrome Along With Clostridium perfringens Bacteremia in a Neurodegenerative Disease Patient: A Case Report.

Leaky gut syndrome (LGS) is caused by intestinal epithelial injury and increased intestinal permeability due to a variety of factors, including chronic stress, inflammatory bowel disease, diabetes, surgery, and chemotherapy, resulting in an increased influx of matter from the intestinal lumen causing constipation and bacteremia. To our knowledge, this is the first known case of LGS along with () bacteremia in a neurodegenerative disease patient. The patient was an 81-year-old male with a history of Alzheimer's disease, cerebral infarction, and diverticulitis in a psychiatric hospital, fed via a nasogastric tube.