Materiały źródłowe

• #1 Ulcerative colitis | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-020-0205-x

  Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown aetiology affecting the colon and rectum. Multiple factors, such as genetic background, environmental and luminal factors, and mucosal immune dysregulation, have been suggested to contribute to UC pathogenesis. […] An improved understanding of the mechanisms underlying UC has led to the emergence of new treatments. […] However, delineating the aetiology of UC is necessary to ultimately achieve disease cure.

• #2 Ulcerative colitis: understanding its cellular pathology could provide insights into novel therapies | Journal of Inflammation | Full Text

  https://journal-inflammation.biomedcentral.com/articles/10.1186/s12950-020-00246-4

  To dissect the molecular basis of UC, it is necessary to have thorough knowledge of the cellular populations that constitute the large intestine. […] Correct functioning of specialized intestinal epithelial cells is essential to maintain intestinal homeostasis and its dysfunction plays a central role in the pathogenesis of several diseases, including UC. […] UC is a multifactorial disorder; genetic predisposition, epithelial barrier defects, dysregulated immune responses and environmental factors play a role in its pathogenesis. […] Although the exact aetiology of UC remains elusive, the commensal luminal flora is known to trigger an inappropriate and overactive mucosal immune response in genetically susceptible individuals, causing intestinal tissue damage. […] Autoantibodies in the mucosa of the large intestine may play a part in the pathogenesis of this disease.

• #3 Ulcerative colitis | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-020-0205-x

  Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown aetiology affecting the colon and rectum. Multiple factors, such as genetic background, environmental and luminal factors, and mucosal immune dysregulation, have been suggested to contribute to UC pathogenesis. […] An improved understanding of the mechanisms underlying UC has led to the emergence of new treatments. […] However, delineating the aetiology of UC is necessary to ultimately achieve disease cure.

• #4 Ulcerative Colitis – Causes – Investigations – Management – TeachMeSurgery 

  https://teachmesurgery.com/general/large-bowel/ulcerative-colitis/

  The pathogenesis of ulcerative colitis is complex and its aetiology remains incompletely understood. Current views suggest that it occurs after environmental exposures in individuals with a genetic predisposition, with epithelial barrier defects, dysregulated immune responses, and dysbiosis being key in initiating and perpetuating inflammation. […] It is characterised by diffuse continual mucosal inflammation of the large bowel, beginning in the rectum and spreading proximally. This can potentially affect the entire large bowel, with up to 20% cases also having terminal ileal involvement, termed backwash ileitis. […] Histological changes include non-granulomatous inflammation of the mucosa and submucosa, crypt abscesses, and goblet cell hypoplasia. Repeated cycles of ulceration and healing may lead to raised areas of inflamed tissue termed pseudopolyps. […] Much like Crohns disease, it appears to have a familial link.

• #5 Ulcerative colitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6487890/

  Ulcerative colitis is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. The pathogenesis is multifactorial, involving genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. […] Colonic epithelial cells (colonocytes), and mucous barrier and epithelial barrier defects are strongly implicated in the pathogenesis of ulcerative colitis. The expression of peroxisome proliferator-activated receptor gamma (PPAR-), a negative regulator of NF-B-dependent inflammation, is reduced in the colonocytes of patients with ulcerative colitis, suggesting a causal link. […] Current evidence implicates both innate and adaptive cellular immunity as key to disease pathogenesis. Earlier evidence suggested that ulcerative colitis is a modified T-helper-2 (Th2) disease, while Crohns disease is Th1 driven. […] Additionally, IL-13 mRNA levels were significantly increased in rectal biopsies from patients with ulcerative colitis compared with patients in the control group. […] The possibility that ILCs might be drivers of disease pathogenesis has led to a number of potential novel therapeutic targets.

• #6

  https://link.springer.com/article/10.1186/s43556-024-00207-w

  Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by abdominal pain, diarrhea, rectal bleeding, and weight loss. The pathogenesis and treatment of UC remain key areas of research interest. Various factors, including genetic predisposition, immune dysregulation, and alterations in the gut microbiota, are believed to contribute to the pathogenesis of UC. […] The etiology of UC is multifactorial, involving complex interactions among genetic predisposition, immune dysregulation, environmental factors, and gut microbiota alterations. […] UC is believed to result from the interaction between genetic susceptibility, immune factors, and gut microbiota alteration, leading to abnormal mucosal immune responses and impaired epithelial barrier function. […] Advances in genetic research have significantly enhanced our understanding of UC’s pathogenesis, revealing crucial insights into the genetic factors that contribute to disease risk and progression.

• #7 Pathogenesis of Ulcerative Colitis and Crohn’s Disease: Sim

  https://www.longdom.org/open-access/pathogenesis-of-ulcerative-colitis-and-crohn8217s-disease-similarities-differences-and-a-lot-of-things-we-do-not-know-ye-49592.html

  Of the 163 identified loci, 110 are linked to both CD and UC, while 30 are specific for CD, and 23 are specific for UC. […] This fact suggests that many, but not all, of the mechanisms playing a role in CD are somewhat involved also in UC. […] Several genes that are associated with both CD and UC play a role in the interleukin (IL)-23 signalling pathway. […] These recent findings have questioned the previous theory of a clear Th2-driven inflammation in UC and Th1-driven responses in CD, and have drawn attention to the role of Th17 lymphocytes in the pathogenesis of both disorders. […] The role of IL-17 was at least partly elucidated by animal experiments, which have suggested that IL-17A protects from intestinal inflammation, while IL-17F promotes it. […] Another example of common susceptibility loci in UC and CD is the IL-10 gene.

• #8

  https://link.springer.com/article/10.1186/s43556-024-00207-w

  Genome-wide association studies (GWAS) have identified numerous genetic loci associated with UC, although these findings are predominantly derived from studies of European populations. […] The presence of perinuclear antineutrophil cytoplasmic antibodies (ANCA) has emerged as a potential biomarker for disease activity. […] The variations in the strength of familial IBD and future risk of IBD in first-degree relatives support differences in genetic predisposition. […] GWAS have been conducted to identify genetic variants associated with UC. […] The putative genes identified through these studies play various roles in gut immunity, including regulating the gut mucosal barrier, autophagy, epithelial restitution, microbial defense, and adaptive immunity. […] UC is a multifactorial autoimmune disease characterized by a dysregulated immune response and impaired epithelial barrier.

• #9 Pathogenesis of Ulcerative Colitis and Crohn’s Disease: Sim

  https://www.longdom.org/open-access/pathogenesis-of-ulcerative-colitis-and-crohn8217s-disease-similarities-differences-and-a-lot-of-things-we-do-not-know-ye-49592.html

  Of the 163 identified loci, 110 are linked to both CD and UC, while 30 are specific for CD, and 23 are specific for UC. […] This fact suggests that many, but not all, of the mechanisms playing a role in CD are somewhat involved also in UC. […] Several genes that are associated with both CD and UC play a role in the interleukin (IL)-23 signalling pathway. […] These recent findings have questioned the previous theory of a clear Th2-driven inflammation in UC and Th1-driven responses in CD, and have drawn attention to the role of Th17 lymphocytes in the pathogenesis of both disorders. […] The role of IL-17 was at least partly elucidated by animal experiments, which have suggested that IL-17A protects from intestinal inflammation, while IL-17F promotes it. […] Another example of common susceptibility loci in UC and CD is the IL-10 gene.

• #10 Ulcerative colitis: understanding its cellular pathology could provide insights into novel therapies | Journal of Inflammation | Full Text

  https://journal-inflammation.biomedcentral.com/articles/10.1186/s12950-020-00246-4

  Dynamic interactions between the gastrointestinal epithelium and the mucosal immune system normally contribute to ensuring intestinal homeostasis and optimal immunosurveillance, but destabilisation of these interactions in genetically predisposed individuals can lead to the development of chronic inflammatory diseases. Ulcerative colitis is one of the main types of inflammatory diseases that affect the bowel, but its pathogenesis has yet to be completely defined. […] Several genetic factors and other inflammation-related genes are implicated in mediating the inflammation and development of the disease. Some susceptibility loci associated with increased risk of ulcerative colitis are found to be implicated in mucosal barrier function. […] UC is a disease of unknown aetiology characterized by inflammation of the mucosa and sub-mucosa of the colon and rectum lining, causing ulcers to develop.

• #11 Pathology Outlines – Ulcerative colitis

  https://www.pathologyoutlines.com/topic/colonuc.html

  Disruption in the homeostatic balance of the mucosal immunity and the enteric nonpathogenic bacteria, resulting in the patient’s aberrant immune response to the enteric commensal bacteria […] Increased number of colonic epithelium activated and mature dendritic cells with increased stimulatory capacity […] Increased expression of TLR4 by lamina propria cells and TLR4 polymorphism, which can alter susceptibility to enteric infections and tolerance to commensal bacteria […] Disruption in the homeostatic balance between regulatory and effector T cells, leading to a nonclassic natural killer T cell production of IL5 and IL13, which have cytotoxic effects on epithelial cells, mediating an atypical Th2 response […] Increase in proinflammatory cytokines, chemoattractants such as CXCL8 and adhesion molecules such as MadCAM1 recruit increased leukocytes to the colonic mucosa […] Other genetic risk loci include IL23 and IL10, JAK2 kinase pathway genes, hepatocyte nuclear factor 4α, CDH1 and laminin β1.

• #12

  https://www.nhs.uk/conditions/ulcerative-colitis/causes/

  It also seems inherited genes may be a factor in the development of ulcerative colitis. […] Researchers have identified several genes that seem to make people more likely to develop ulcerative colitis. […] It’s believed many of these genes play a role in the immune system. […] Where and how you live also seems to affect your chances of developing ulcerative colitis, which suggests environmental factors are important. […] Various environmental factors that may be linked to ulcerative colitis have been studied, including air pollution, medicine and certain diets. […] This suggests that reduced exposure to bacteria may be an important factor.

• #13 Ulcerative Colitis: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/183084-overview

  The exact etiology of UC is unknown, but the disease appears to be multifactorial and polygenic. The proposed causes include environmental factors, immune dysfunction, and a likely genetic predisposition. […] Histocompatibility human leukocyte antigen (HLA)B27 is identified in most patients with UC, although this finding is not causally associated with the condition and the finding of HLA-B27 does not imply a substantially increased risk for UC. UC may also be influenced by diet, although diet is thought to play a secondary role. Food or bacterial antigens might exert an effect on the already damaged mucosal lining, which has increased permeability. […] UC is a diffuse, nonspecific inflammatory disease whose etiology is unknown. The colonic mucosa proximal from the rectum is persistently affected, frequently involving erosions and/or ulcers, as well as involving repeated cycles of relapse and remission and potential extraintestinal manifestations.

• #14 Pathogenesis of Ulcerative Colitis and Crohn’s Disease: Sim

  https://www.longdom.org/open-access/pathogenesis-of-ulcerative-colitis-and-crohn8217s-disease-similarities-differences-and-a-lot-of-things-we-do-not-know-ye-49592.html

  Large number of studies have found a highly significant negative association between appendectomy and UC. […] Dietary intake has dramatically shifted to a high-fat, high-carbohydrate diet in Western countries in the last decades, which is thought to increase the risk of several chronic illnesses. […] Recent evidence has made it clear that changes in diet can induce significant modifications in the components of the colonic microbial flora. […] Vitamin-D deficiency in IBD could be the consequence of the disease itself, due to insufficient intake, malabsorption, reduced sunlight exposure and low physical activity. […] Some medications are suspected to participate in the development and in relapses of IBD. […] The next group of medications implicated in the pathogenesis of IBD are the non-steroid anti-inflammatory drugs (NSAIDs).

• #15 Ulcerative Colitis Pathology: Overview, Epidemiology, Etiology

  https://emedicine.medscape.com/article/2005396-overview

  One theory proposes that UC occurs as a direct result of an aberrant immune response to „gut luminal antigen” in a genetically susceptible host. […] Environmental factors, such as Westernization (urban lifestyle, pollution, diet, antibiotics, and hygiene), are linked to an increased incidence of UC. […] An impaired epithelial barrier is a key pathogenic factor in UC, involving altered secretion of antimicrobial peptides and physical defects in tight junctions. This barrier dysfunction, combined with genetic susceptibility and environmental triggers, contributes to the onset of UC. […] In summary, research and literature indicate that when genetic predisposition is combined with certain environmental factors both in the external and internal environment and acted upon by an altered immune response, IBD may result.

• #16 Ulcerative Colitis | Calgary Guide

  https://calgaryguide.ucalgary.ca/ulcerative-colitis-clinical-findings/ulcerative-colitis/

  Inflammation is systemic, affecting: Environmental Factors Diet, bacteria/viruses, drugs Genetic Susceptibility Behavioral Factors: In UC, smoking and appendectomy are actually protective (unknown reason) Immune response against the GI tract. (Unclear mechanism, but thought to be mediated by cytokine release and neutrophil infiltration) […] Inflammation of the GI tract epithelial lining Starting at the rectum and moves up the colon and is continuous (does not invade the small intestine) […] Inflammation affects the mucosal and submucosal only […] Inflammation permeability of the blood vessels supplying the GI tract wall Fluid leak out of capillaries into GI tract wall, causes edema and swelling […] Inflammation, ulceration, or infection at the anus (all involve the RECTUM!) […] Tenesmus, urgency, frequency (feeling or urgency to defecate, but little stool is produced) […] More sodium (and thus water) is retained in the GI tract lumen […] Uveitis Iritis, scleritis Sclerosing Cholangitis Autoimmune hemolytic anemia.

• #17 Pathogenesis of Ulcerative Colitis and Crohn’s Disease: Sim

  https://www.longdom.org/open-access/pathogenesis-of-ulcerative-colitis-and-crohn8217s-disease-similarities-differences-and-a-lot-of-things-we-do-not-know-ye-49592.html

  The biodiversity of active bacteria is reduced in UC patients compared to controls. […] A decreased number of gastrointestinal health-promoting bacteria, Bacteroidetes and Lachnospiraceae, were found in surgical specimens from UC patients by rRNA sequence analysis compared to controls. […] Smoking is the most studied environmental factor in IBD, and is also a particular factor where CD and UC clearly split up. […] The first report on non-smoking as a risk factor in UC was published in 1982, and several more have confirmed this observation. […] The appendix is an important lymphoid organ along the gastrointestinal tract, which helps to maintain the healthy gut microbial flora by modulating the epithelial regeneration and protecting from pathogen microbes via the production of biofilms and compounds such as mucin and IgA.

• #18

  https://link.springer.com/article/10.1007/s10787-007-1563-7

  Although human appendix has been considered as a vestigial remnant, recent observations have focused attention on the role of the appendix in the pathogenesis of ulcerative colitis (UC). […] Many case-control studies suggest that previous appendectomy is rare in UC patients. This inverse relation is limited to patients who undergo appendectomy before the age of 20 years. […] Moreover, several investigators reported the improvement of UC after appendectomy, especially in young patients. […] In the appendix of UC patients, the CD4/CD8 ratio is significantly increased, and the proportion of CD4+CD69+ (early activation antigen) T cells, but not of CD4+HLA-DR+ (mature activation antigen) T cells, is also significantly increased. […] These findings suggest that the appendix may be a priming site in the development of UC. […] Further studies including analysis of CD4+ and CD8+ T cells are necessary to clarify the role of the appendix in the pathogenesis of UC.

• #19 Frontiers | The mechanism of traditional medicine in alleviating ulcerative colitis: regulating intestinal barrier function

  https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1228969/full

  The intestinal barrier plays an essential role in maintaining the gut homeostasis. Some studies have disclosed that the disruption of the barrier function or alterations in its structure is closely associated with the development of many intestinal diseases, including UC. […] Many recent studies have revealed that some traditional decoctions or herbal plant-derived compounds may have a role in protecting the maintenance of intestinal barrier integrity and thereby preventing the development and progression of experimental colitis. […] The protective effects of the decoctions/compounds on intestinal barrier function are revealed to be associated with the activation of numerous signaling pathways, which regulate the alteration of metabolism processes and microbiota compositions. […] As mentioned above, a large body of evidence has been provided by recent studies to prove the effects of traditional decoctions, formulas, some herbal plants, and naturally occurring compounds on alleviating UC-associated colitis via various mechanisms.

• #20 Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis | Gut

  https://gut.bmj.com/content/68/12/2142

  Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis. […] The aim of this study was to determine the underlying compositional alterations, their molecular background and potential contribution to UC pathogenesis. […] Core mucus structural components were reduced in active UC. […] Thus, mucus abnormalities are likely to contribute to UC pathogenesis. […] The reduction in mucus core proteins precedes inflammation and is associated with interleukin 18 activation. […] Our observations indicate that mucus barrier weakening is common in active UC, occurs independent of local inflammation and likely plays a role in UC pathogenesis. […] The most striking finding of this study was a reduction of mucus core structural components in patients with UC with ongoing inflammation.

• #21 Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis | Gut

  https://gut.bmj.com/content/68/12/2142

  Our findings suggest that mucus barrier weakening is associated with exhaustion of the sentinel goblet cell response to microbial challenge. […] The observed mucus abnormalities were not secondary to local inflammation, suggesting that they may instead precede and contribute to activation of the disease.

• #22 Pathology Outlines – Ulcerative colitis

  https://www.pathologyoutlines.com/topic/colonuc.html

  Idiopathic chronic inflammatory disorder of the colon mucosa […] Generally starts in the rectum and extends proximally in a continuous pattern […] Complex multifactorial process involving an overwhelming T helper type 2-like immune response, leading to mucosal injury in response to gut microbial dysbiosis in genetically predisposed patients […] Not fully known but appears to be a complex multifactorial process involving an overwhelming T helper type 2-like immune response, leading to mucosal injury in response to gut microbial dysbiosis in genetically predisposed patients […] Proposed mechanisms include: Damage to the colonic epithelial barrier due to dysregulation of epithelial tight junctions, which provide a physical barrier between the immune cells and the luminal microbes, leads to increased permeability

• #23 Ulcerative Colitis Pathology: Overview, Epidemiology, Etiology

  https://emedicine.medscape.com/article/2005396-overview

  One theory proposes that UC occurs as a direct result of an aberrant immune response to „gut luminal antigen” in a genetically susceptible host. […] Environmental factors, such as Westernization (urban lifestyle, pollution, diet, antibiotics, and hygiene), are linked to an increased incidence of UC. […] An impaired epithelial barrier is a key pathogenic factor in UC, involving altered secretion of antimicrobial peptides and physical defects in tight junctions. This barrier dysfunction, combined with genetic susceptibility and environmental triggers, contributes to the onset of UC. […] In summary, research and literature indicate that when genetic predisposition is combined with certain environmental factors both in the external and internal environment and acted upon by an altered immune response, IBD may result.

• #24 The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis—A Literature Review

  https://www.mdpi.com/2227-9059/11/12/3144

  Abnormal activation of PRRs against commensal bacteria plays a major role in IBD etiology. […] Macrophages also contribute to UC pathogenesis as they mediate microbial defense and are involved in interactions between IBD and the microbiome, though the mechanism is not yet well understood. […] The intestinal barrier of patients with UC presents reduced mucus layer and goblet cells compared to the healthy gut, resulting in increased intestinal permeability.

• #25 Reddit – The heart of the internet

  https://www.reddit.com/r/UlcerativeColitis/comments/1j640x9/uncertain_pathogenesis_of_ulcerative_colitis/

  The pathogenesis of ulcerative colitis (UC) is primarily driven by epithelial barrier dysfunction, innate and adaptive immune dysregulation, and excessive inflammatory responses. […] Reduced expression of tight junction proteins such as Claudin-1, Occludin, and ZO-1 increases intestinal permeability. […] The mucus layer becomes thinner, with a significant decrease in MUC2 production, impairing mucosal protection. […] Bacterial antigens from the gut lumen penetrate the epithelium into the lamina propria, triggering immune activation. […] UC is predominantly a Th2-mediated disease, where epithelial cells produce IL-13, playing a crucial role. […] IL-13 increases epithelial apoptosis, disrupts mucus production, and weakens the barrier function. […] The immune response in UC is characterized by a dominant Th2/IL-13 axis, epithelial barrier disruption, excessive neutrophil infiltration, and sustained pro-inflammatory cytokine release, collectively driving the chronic inflammation and mucosal damage seen in the disease.

• #26 Reddit – The heart of the internet

  https://www.reddit.com/r/UlcerativeColitis/comments/1j640x9/uncertain_pathogenesis_of_ulcerative_colitis/

  The pathogenesis of ulcerative colitis (UC) is primarily driven by epithelial barrier dysfunction, innate and adaptive immune dysregulation, and excessive inflammatory responses. […] Reduced expression of tight junction proteins such as Claudin-1, Occludin, and ZO-1 increases intestinal permeability. […] The mucus layer becomes thinner, with a significant decrease in MUC2 production, impairing mucosal protection. […] Bacterial antigens from the gut lumen penetrate the epithelium into the lamina propria, triggering immune activation. […] UC is predominantly a Th2-mediated disease, where epithelial cells produce IL-13, playing a crucial role. […] IL-13 increases epithelial apoptosis, disrupts mucus production, and weakens the barrier function. […] The immune response in UC is characterized by a dominant Th2/IL-13 axis, epithelial barrier disruption, excessive neutrophil infiltration, and sustained pro-inflammatory cytokine release, collectively driving the chronic inflammation and mucosal damage seen in the disease.

• #27 Ulcerative colitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6487890/

  Ulcerative colitis is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. The pathogenesis is multifactorial, involving genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. […] Colonic epithelial cells (colonocytes), and mucous barrier and epithelial barrier defects are strongly implicated in the pathogenesis of ulcerative colitis. The expression of peroxisome proliferator-activated receptor gamma (PPAR-), a negative regulator of NF-B-dependent inflammation, is reduced in the colonocytes of patients with ulcerative colitis, suggesting a causal link. […] Current evidence implicates both innate and adaptive cellular immunity as key to disease pathogenesis. Earlier evidence suggested that ulcerative colitis is a modified T-helper-2 (Th2) disease, while Crohns disease is Th1 driven. […] Additionally, IL-13 mRNA levels were significantly increased in rectal biopsies from patients with ulcerative colitis compared with patients in the control group. […] The possibility that ILCs might be drivers of disease pathogenesis has led to a number of potential novel therapeutic targets.

• #28 Frontiers | The mechanism of traditional medicine in alleviating ulcerative colitis: regulating intestinal barrier function

  https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1228969/full

  Ulcerative colitis (UC) is an idiopathic inflammatory disease mainly affects the large bowel and the rectum. The pathogenesis of this disease has not been fully elucidated, while the disruption of the intestinal barrier function triggered by various stimulating factors related to the host genetics, immunity, gut microbiota, and environment has been considered to be major mechanisms that affect the development of UC. […] An increasing body of evidence showed that the pathogenesis of UC is associated with the interplay of multiple factors from host genetics, immunity, microbes, and the environment. […] The initiation of UC may be triggered by particular environmental factors, such as medications, smoking, and stress, which induce disruption of intestinal barrier integrity. […] The microbes in the gut may then invade into lamina propria through the damaged intestinal epithelial barrier and stimulate the local inflammatory cells, such as the tissue-resident macrophages and intestinal dendritic cells, which subsequently release pro-inflammatory cytokines and chemokines to recruit other types of inflammatory cells, such as lymphocytes and neutrophils to the inflammatory sites.

• #29 Ulcerative Colitis : Pathogenesis-II

  https://www.webpathology.com/images/gastrointestinal/large-bowel/inflammatory-bowel-disease/42416

  The etiology of inflammatory bowel disease is unknown; however, there appears to be a complex interplay of genetic susceptibility, host immunity, and environmental factors. Several pathways are involved, including: Inappropriate mucosal immune responses to gut bacteria are considered to play a key role in the pathogenesis of IBD. Inflammatory cytokines such as TNF, interferon- and IL-13 are involved in the pathogenesis of IBD. Given the central role played by defective immune responses in the development of Crohn disease and UC, immunosuppressive agents are a key component of therapeutic regimens. A number of epithelial defects have been found in Crohn disease and UC, including defective barrier function of intestinal epithelial tight junction. In addition, UC is associated with polymorphisms involving ECM1 (extracellular matrix protein 1) and transcription factor HNFA. According to one model of IBD pathogenesis, defective barrier function at intestinal epithelial tight junctions allows bacterial components to access lamina propria and activate innate and adaptive immune responses. The release of TNF and other cytokines increases tight junction permeability which allows even greater amount of bacterial components. This sets up repeated cycles of cytokine-induced mucosal damage, inflammation and ulceration followed by regeneration and healing.

• #30 Ulcerative colitis: understanding its cellular pathology could provide insights into novel therapies | Journal of Inflammation | Full Text

  https://journal-inflammation.biomedcentral.com/articles/10.1186/s12950-020-00246-4

  There is also considerable evidence that defective mucosal immunoregulation, including abnormal changes of T cells, B cells, granulocytes, macrophages and the cytokines and chemokines produced by these cells, plays a major role in UC pathogenesis. […] Elevated mononuclear phagocyte populations in UC colonic mucosa could partly explain why some UC patients respond well to infliximab and vedolizumab treatment and others do not.

• #31 The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis—A Literature Review

  https://www.mdpi.com/2227-9059/11/12/3144

  The gut microbiome plays an essential role in the progression of inflammation. Dysfunction in interactions between gut microbiota and epithelial cells have a significant role in UC pathogenesis. […] The mucus barrier overlying the epithelium is a crucial element in providing an environment for commensal microbes’ colonization. Abnormalities in its structure play a significant role in inflammation onset. […] The mutual impact between the host’s immune system and microbes is possible due to pattern-recognition receptors (PRRs) such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), mannose-binding receptors, complement receptors and C-type lectin receptors (CLRs) expressed on the intestinal epithelial cells and innate immune cells. […] Activation and translocation of NF-κB mediated by MAMPs/PAMPs promote the expression of inflammatory genes but also genes involved in tissue repair, regeneration, and angiogenesis.

• #32 Pathology Outlines – Ulcerative colitis

  https://www.pathologyoutlines.com/topic/colonuc.html

  Disruption in the homeostatic balance of the mucosal immunity and the enteric nonpathogenic bacteria, resulting in the patient’s aberrant immune response to the enteric commensal bacteria […] Increased number of colonic epithelium activated and mature dendritic cells with increased stimulatory capacity […] Increased expression of TLR4 by lamina propria cells and TLR4 polymorphism, which can alter susceptibility to enteric infections and tolerance to commensal bacteria […] Disruption in the homeostatic balance between regulatory and effector T cells, leading to a nonclassic natural killer T cell production of IL5 and IL13, which have cytotoxic effects on epithelial cells, mediating an atypical Th2 response […] Increase in proinflammatory cytokines, chemoattractants such as CXCL8 and adhesion molecules such as MadCAM1 recruit increased leukocytes to the colonic mucosa […] Other genetic risk loci include IL23 and IL10, JAK2 kinase pathway genes, hepatocyte nuclear factor 4α, CDH1 and laminin β1.

• #33 The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis—A Literature Review

  https://www.mdpi.com/2227-9059/11/12/3144

  The gut microbiome plays an essential role in the progression of inflammation. Dysfunction in interactions between gut microbiota and epithelial cells have a significant role in UC pathogenesis. […] The mucus barrier overlying the epithelium is a crucial element in providing an environment for commensal microbes’ colonization. Abnormalities in its structure play a significant role in inflammation onset. […] The mutual impact between the host’s immune system and microbes is possible due to pattern-recognition receptors (PRRs) such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), mannose-binding receptors, complement receptors and C-type lectin receptors (CLRs) expressed on the intestinal epithelial cells and innate immune cells. […] Activation and translocation of NF-κB mediated by MAMPs/PAMPs promote the expression of inflammatory genes but also genes involved in tissue repair, regeneration, and angiogenesis.

• #34 The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis—A Literature Review

  https://www.mdpi.com/2227-9059/11/12/3144

  Abnormal activation of PRRs against commensal bacteria plays a major role in IBD etiology. […] Macrophages also contribute to UC pathogenesis as they mediate microbial defense and are involved in interactions between IBD and the microbiome, though the mechanism is not yet well understood. […] The intestinal barrier of patients with UC presents reduced mucus layer and goblet cells compared to the healthy gut, resulting in increased intestinal permeability.

• #35 Host–Viral Interactions in the Pathogenesis of Ulcerative Colitis

  https://www.mdpi.com/1422-0067/22/19/10851

  TLR-mediated innate immune dysfunction has recently been implicated in the pathogenesis of UC. […] Results from animal studies report a role for RIG-I and MDA5 in colitis development although their specific involvement is still poorly understood. […] Dysregulated inflammasome activation is linked to inflammatory disorders. […] The NLRP3 inflammasome manages innate immune responses, contributing to the ongoing inflammation and the disruption of the mucosal barrier through the modification of tight junction proteins and cell apoptosis. […] During the active UC mucosal mRNA expression of NLRP3, the inflammasome components NLRP3, IL-1β, ASC, and Caspase-1 are increased, correlating with disease activity. […] IL-18 has both a protective and detrimental role in colonic inflammation. […] Increased NLRP6 inflammasome activity and IL-18 levels in the colonic mucosa due to deficiencies in the regulatory mechanisms controlled by CYLD, result in severe colitis in mice. […] Overall, several recent findings have indicated that responses to certain viruses might be involved in UC pathogenesis. […] Our finding that the IFN signature genes are upregulated in IECs during active IBD suggests that responses to viruses might be involved in the pathogenesis of IBD.

• #36 Host–Viral Interactions in the Pathogenesis of Ulcerative Colitis

  https://www.mdpi.com/1422-0067/22/19/10851

  TLR-mediated innate immune dysfunction has recently been implicated in the pathogenesis of UC. […] Results from animal studies report a role for RIG-I and MDA5 in colitis development although their specific involvement is still poorly understood. […] Dysregulated inflammasome activation is linked to inflammatory disorders. […] The NLRP3 inflammasome manages innate immune responses, contributing to the ongoing inflammation and the disruption of the mucosal barrier through the modification of tight junction proteins and cell apoptosis. […] During the active UC mucosal mRNA expression of NLRP3, the inflammasome components NLRP3, IL-1β, ASC, and Caspase-1 are increased, correlating with disease activity. […] IL-18 has both a protective and detrimental role in colonic inflammation. […] Increased NLRP6 inflammasome activity and IL-18 levels in the colonic mucosa due to deficiencies in the regulatory mechanisms controlled by CYLD, result in severe colitis in mice. […] Overall, several recent findings have indicated that responses to certain viruses might be involved in UC pathogenesis. […] Our finding that the IFN signature genes are upregulated in IECs during active IBD suggests that responses to viruses might be involved in the pathogenesis of IBD.

• #37 Ulcerative colitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6487890/

  Ulcerative colitis is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. The pathogenesis is multifactorial, involving genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. […] Colonic epithelial cells (colonocytes), and mucous barrier and epithelial barrier defects are strongly implicated in the pathogenesis of ulcerative colitis. The expression of peroxisome proliferator-activated receptor gamma (PPAR-), a negative regulator of NF-B-dependent inflammation, is reduced in the colonocytes of patients with ulcerative colitis, suggesting a causal link. […] Current evidence implicates both innate and adaptive cellular immunity as key to disease pathogenesis. Earlier evidence suggested that ulcerative colitis is a modified T-helper-2 (Th2) disease, while Crohns disease is Th1 driven. […] Additionally, IL-13 mRNA levels were significantly increased in rectal biopsies from patients with ulcerative colitis compared with patients in the control group. […] The possibility that ILCs might be drivers of disease pathogenesis has led to a number of potential novel therapeutic targets.

• #38 Cytokines in the Pathogenesis of Ulcerative Colitis – Giorgos Bamias – Discovery Medicine

  https://www.discoverymedicine.com/Giorgos-Bamias/2011/05/23/cytokines-in-the-pathogenesis-of-ulcerative-colitis/

  Based on the studies mentioned above, a pathogenetic scheme has been proposed for the involvement of IL-13 in UC pathogenesis. According to this theory, unidentified stimuli, most probably commensal flora-derived microbial products, stimulate atypical NKT cells to produce IL-13 in the colonic mucosa. The downstream effects culminate to epithelial injury as a result of the cytotoxic activity of NKT cells on epithelial cells, the IL-13 induced apoptosis of colonocytes, and the overall disruption of tight junctions. This pathogenetic scheme fits with the pathological phenotype of injury in UC that consists of extensive destruction of the colonic epithelial layer. […] A proof of principle for this proposed pathogenetic role of IL-13 in UC-associated intestinal inflammation is provided by a recent study that reported a positive correlation between effective anti-inflammatory treatment and mucosal and/or systemic levels of the cytokine.

• #39 Ulcerative colitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6487890/

  Ulcerative colitis is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. The pathogenesis is multifactorial, involving genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. […] Colonic epithelial cells (colonocytes), and mucous barrier and epithelial barrier defects are strongly implicated in the pathogenesis of ulcerative colitis. The expression of peroxisome proliferator-activated receptor gamma (PPAR-), a negative regulator of NF-B-dependent inflammation, is reduced in the colonocytes of patients with ulcerative colitis, suggesting a causal link. […] Current evidence implicates both innate and adaptive cellular immunity as key to disease pathogenesis. Earlier evidence suggested that ulcerative colitis is a modified T-helper-2 (Th2) disease, while Crohns disease is Th1 driven. […] Additionally, IL-13 mRNA levels were significantly increased in rectal biopsies from patients with ulcerative colitis compared with patients in the control group. […] The possibility that ILCs might be drivers of disease pathogenesis has led to a number of potential novel therapeutic targets.

• #40

  https://link.springer.com/article/10.1186/s43556-024-00207-w

  Immune dysfunction in UC involves both innate and adaptive immune systems. […] In the case of UC, mature dendritic cells become more sensitive and activated, indicating their significant involvement in generating inflammation. […] Crypt scarring in UC results from inflammatory cell infiltration, including neo-lymphotropic and T-lymphocytes, causing damage to epithelial cells. […] The imbalance between Th17 cells and Treg cells was found to be a crucial factor in the pathogenesis of UC. […] The potential immune mechanisms of UC include impacting the innate and adaptive immune response by the influence of the DCs function, dysregulation of the Treg/Th cells, promotion of pro-inflammatory factor secretion, reduction of anti-inflammatory factor secretion. […] The intricate balance between pro-inflammatory and anti-inflammatory mechanisms is central to the development and progression of ulcerative colitis.

• #41 Pathogenesis of Ulcerative Colitis and Crohn’s Disease: Sim

  https://www.longdom.org/open-access/pathogenesis-of-ulcerative-colitis-and-crohn8217s-disease-similarities-differences-and-a-lot-of-things-we-do-not-know-ye-49592.html

  Of the 163 identified loci, 110 are linked to both CD and UC, while 30 are specific for CD, and 23 are specific for UC. […] This fact suggests that many, but not all, of the mechanisms playing a role in CD are somewhat involved also in UC. […] Several genes that are associated with both CD and UC play a role in the interleukin (IL)-23 signalling pathway. […] These recent findings have questioned the previous theory of a clear Th2-driven inflammation in UC and Th1-driven responses in CD, and have drawn attention to the role of Th17 lymphocytes in the pathogenesis of both disorders. […] The role of IL-17 was at least partly elucidated by animal experiments, which have suggested that IL-17A protects from intestinal inflammation, while IL-17F promotes it. […] Another example of common susceptibility loci in UC and CD is the IL-10 gene.

• #42 Mount Sinai Researchers Start to Unravel B Cell Dysregulation in Ulcerative Colitis

  https://reports.mountsinai.org/article/gi2023-03-b-cells-and-ulcerative-colitis

  Mount Sinai-led researchers have discovered for the first time a highly dysregulated B cell response in ulcerative colitis that opens the door to potential new biomarkers and therapeutic strategies for it as well as other types of inflammatory bowel disease. […] While T cells have received abundant attention from scientists probing the pathogenesis of ulcerative colitis (UC), B cells a major component of the adaptive immune system have remained largely unstudied in this context. […] Weve begun to define the landscape of B cells during UC-associated intestinal inflammation, and found major perturbations within the mucosal B cell compartment, says Saurabh Mehandru, MD, Professor of Medicine (Gastroenterology) at the Icahn School of Medicine at Mount Sinai and senior author of the study. […] These changes include a significant expansion of nave B cells and IgG+ plasma cells, along with an expansion of gut-homing plasma cells that correlate with disease activity and predict disease complications.

• #43 Mount Sinai Researchers Start to Unravel B Cell Dysregulation in Ulcerative Colitis

  https://reports.mountsinai.org/article/gi2023-03-b-cells-and-ulcerative-colitis

  With their sights set on the origins of the dysregulated B cell response to ulcerative colitis, the researchers surfaced some important new findings about IgG+-producing plasma cells that have been identified in the diseased intestinal mucosa. […] A case in point highlighted by the Mount Sinai team is a population of interferon (IFN)-primed nave B cells that expands in UC and is associated with an increased frequency of IgG+ plasmablasts and IgG+ plasma cells. […] That gives us an important window into why IgG+ plasma cells may potentially be increased in UC. […] Taken together, says Dr. Mehandru, these data provide compelling evidence for type 1 immunity as a driver of nave B cell molecular imprinting as well as skewing of acute B cell responses toward IgG+ production in the intestines of people with ulcerative colitis. […] On a broader scale, Dr. Mehandru believes his teams research has begun to identify the biology and mechanisms behind B cell dysregulation a breakthrough that could lead to promising therapeutic targets designed to help millions of people worldwide who experience ulcerative colitis and IBD.

• #44 The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis—A Literature Review

  https://www.mdpi.com/2227-9059/11/12/3144

  Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum. UC’s pathogenesis involves colonic epithelial cell abnormalities and mucosal barrier dysfunction, leading to recurrent mucosal inflammation. […] The pathogenesis of UC is associated with abnormalities in colonic epithelial cells, the mucus barrier, and the epithelial barrier with a recurring pattern of mucosal inflammation spreading from the rectal region to the upper parts of the colon. […] Dysbiosis of the gut microbiota is a critical contributor to UC development, typically featuring diminished bacterial diversity in the intestines. […] Patients suffering from UC exhibit reduced gut microbiota diversity, a decreased prevalence of Firmicutes, and elevated rates of Gamma-proteobacteria and Enterobacteriaceae.

• #45 The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis—A Literature Review

  https://www.mdpi.com/2227-9059/11/12/3144

  Dysbiosis of the gut microbiota, denoting a perturbation in the equilibrium of the bacterial microflora, emerges as a potent causative determinant in the pathogenesis of chronic diseases, such as metabolic diseases, autoimmune diseases, necrotizing enterocolitis, skin diseases, Crohn’s disease and ulcerative colitis. […] It has been discerned that individuals afflicted with Inflammatory Bowel Disease (IBD) manifest more pronounced variations in the composition of their gut microbiota. […] A significant decrease in beneficial intestinal bacteria (Bifidobacterium longum, Eubacterium rectale, Faecalibacterium prausnitzii, Roseburia intestinalis), as well as enrichment in several harmful bacteria, connected to intestinal inflammation and alterations of epithelial cells permeability, has been recognized in patients with ulcerative colitis.

• #46

  https://link.springer.com/article/10.1186/s43556-024-00207-w

  Key cytokines, such as IL-6 and IL-22, along with regulatory immune cells, including Th17, Treg, and Breg cells, play significant roles in modulating the inflammatory response and maintaining mucosal integrity. […] Significant alterations in gut microbiota, known as microbial dysbiosis, are observed, characterized by reduced diversity in the phyla Firmicutes and Bacteroidetes, alongside an increase in Enterobacteriaceae. […] The reduction in SCFAs contributes to heightened inflammation and compromised gut barrier function. […] FMT can improve the intestinal microbiota, which is considered to have the potential to treat UC.

• #47 The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis—A Literature Review

  https://www.mdpi.com/2227-9059/11/12/3144

  Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum. UC’s pathogenesis involves colonic epithelial cell abnormalities and mucosal barrier dysfunction, leading to recurrent mucosal inflammation. […] The pathogenesis of UC is associated with abnormalities in colonic epithelial cells, the mucus barrier, and the epithelial barrier with a recurring pattern of mucosal inflammation spreading from the rectal region to the upper parts of the colon. […] Dysbiosis of the gut microbiota is a critical contributor to UC development, typically featuring diminished bacterial diversity in the intestines. […] Patients suffering from UC exhibit reduced gut microbiota diversity, a decreased prevalence of Firmicutes, and elevated rates of Gamma-proteobacteria and Enterobacteriaceae.

• #48 The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis—A Literature Review

  https://www.mdpi.com/2227-9059/11/12/3144

  Dysbiosis of the gut microbiota, denoting a perturbation in the equilibrium of the bacterial microflora, emerges as a potent causative determinant in the pathogenesis of chronic diseases, such as metabolic diseases, autoimmune diseases, necrotizing enterocolitis, skin diseases, Crohn’s disease and ulcerative colitis. […] It has been discerned that individuals afflicted with Inflammatory Bowel Disease (IBD) manifest more pronounced variations in the composition of their gut microbiota. […] A significant decrease in beneficial intestinal bacteria (Bifidobacterium longum, Eubacterium rectale, Faecalibacterium prausnitzii, Roseburia intestinalis), as well as enrichment in several harmful bacteria, connected to intestinal inflammation and alterations of epithelial cells permeability, has been recognized in patients with ulcerative colitis.

• #49 Ulcerative Colitis: Pathogenesis

  https://www.eurekaselect.com/article/19807

  The pathogenesis of ulcerative is still poorly understood. […] With the introduction of new culture-independent techniques the research on the intestinal microbiota has revealed an important reduction of Bacteroidetes and Firmicutes leading to a reduced biodiversity and dysbiosis in these patients. […] A dysregulated immune response involving the innate (e.g. toll-like receptors, dendritic cells, etc) and the adaptive immune system (e.g. effector T-cells, regulatory T-cells, eosinophils, neutrophils, etc) may follow or precede the macroscopic lesions. […] The immune response in ulcerative colitis is represented principally by secretion of interleukin-5 and -13 being the latter responsible for the direct cytotoxicity against the epithelial cells. […] Finally, human ulcerative colitis is characterized by the presence of various types of autoantibodies including pANCA, antibodies against goblet cells and the isoforms 1 and 5 of human tropomyosin. The pathogenic potential of these antibodies is still debated.

• #50 Ulcerative colitis – Wikipedia

  https://en.wikipedia.org/wiki/Ulcerative_colitis

  Ulcerative colitis is an autoimmune disease characterized by T-cells infiltrating the colon. No direct causes for UC are known, but factors such as genetics, environment, and an overactive immune system play a role. […] Theories involve immune system dysfunction, genetics, changes in the normal gut bacteria, and environmental factors. […] An increased amount of colonic sulfate-reducing bacteria has been observed in some people with ulcerative colitis, resulting in higher concentrations of the toxic gas hydrogen sulfide. […] Other proposed mechanisms driving the pathophysiology of ulcerative colitis involve an abnormal immune response to the normal gut microbiota. This involves abnormal activity of antigen presenting cells (APCs) including dendritic cells and macrophages. […] However, in ulcerative colitis, aberrant activity of dendritic cells and macrophages results in them phagocytosing bacteria of the normal gut microbiome.

• #51

  https://link.springer.com/article/10.1186/s43556-024-00207-w

  Key cytokines, such as IL-6 and IL-22, along with regulatory immune cells, including Th17, Treg, and Breg cells, play significant roles in modulating the inflammatory response and maintaining mucosal integrity. […] Significant alterations in gut microbiota, known as microbial dysbiosis, are observed, characterized by reduced diversity in the phyla Firmicutes and Bacteroidetes, alongside an increase in Enterobacteriaceae. […] The reduction in SCFAs contributes to heightened inflammation and compromised gut barrier function. […] FMT can improve the intestinal microbiota, which is considered to have the potential to treat UC.

• #52 Frontiers | The mechanism of traditional medicine in alleviating ulcerative colitis: regulating intestinal barrier function

  https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1228969/full

  A study by Shi et al. (2021) found that the effect of Aloe vera on colitis had a relation to its role in regulating mucus production. […] Studies have shown that dysregulation of mucins is closely associated with the development of IBD. […] The gut microbiota may release some metabolites, such as bile acids and short-chain fatty acids (SCFA), which serve as the nutrients of some bacteria and also have a role in regulating the composition of the microbiota. […] The effect of traditional medicine on colitis via targeting microbiota was also proved by other studies of traditional decoctions. […] The maintenance of the intestinal epithelial barrier requires a balance of pro- and anti-inflammatory mediators in the gut. […] Thus, inhibiting immune cell infiltration and inflammatory mediators and thereby restoring the intestinal barrier integrity is an effective strategy for treating UC.

• #53 Mechanisms of Disease: pathogenesis of Crohn’s disease and ulcerative colitis | Nature Reviews Gastroenterology & Hepatology

  https://www.nature.com/articles/ncpgasthep0528

  Chronic intestinal inflammation requires the presence of commensal enteric bacteria and activated T lymphocytes. […] Patients with inflammatory bowel diseases and rodents with chronic intestinal inflammation exhibit loss of immunologic tolerance to normal enteric bacteria. […] Defective innate immune responses can lead to lack of clearance of invading bacteria and to the activation of pathogenic T cells.

• #54 Ulcerative colitis – Wikipedia

  https://en.wikipedia.org/wiki/Ulcerative_colitis

  Ulcerative colitis is an autoimmune disease characterized by T-cells infiltrating the colon. No direct causes for UC are known, but factors such as genetics, environment, and an overactive immune system play a role. […] Theories involve immune system dysfunction, genetics, changes in the normal gut bacteria, and environmental factors. […] An increased amount of colonic sulfate-reducing bacteria has been observed in some people with ulcerative colitis, resulting in higher concentrations of the toxic gas hydrogen sulfide. […] Other proposed mechanisms driving the pathophysiology of ulcerative colitis involve an abnormal immune response to the normal gut microbiota. This involves abnormal activity of antigen presenting cells (APCs) including dendritic cells and macrophages. […] However, in ulcerative colitis, aberrant activity of dendritic cells and macrophages results in them phagocytosing bacteria of the normal gut microbiome.

• #55 Ulcerative colitis – Wikipedia

  https://en.wikipedia.org/wiki/Ulcerative_colitis

  After phagocytosing the microbe, the APCs then enter the mesenteric lymph nodes where they present antigens to naive T-cells while also releasing the pro-inflammatory cytokines IL-12 and IL-23 which lead to T cell differentiation into Th1 and Th17 T-cells. […] T-cell mediated inflammation is thought to be driven by the JAK-STAT intracellular T-cell signaling pathway, leading to the transcription, translation and release of inflammatory cytokines.

• #56 Ulcerative colitis – Wikipedia

  https://en.wikipedia.org/wiki/Ulcerative_colitis

  After phagocytosing the microbe, the APCs then enter the mesenteric lymph nodes where they present antigens to naive T-cells while also releasing the pro-inflammatory cytokines IL-12 and IL-23 which lead to T cell differentiation into Th1 and Th17 T-cells. […] T-cell mediated inflammation is thought to be driven by the JAK-STAT intracellular T-cell signaling pathway, leading to the transcription, translation and release of inflammatory cytokines.

• #57 Host–Viral Interactions in the Pathogenesis of Ulcerative Colitis

  https://www.mdpi.com/1422-0067/22/19/10851

  Emerging evidence indicates that these viruses play a role in human health and may, in turn, have beneficial and/or damaging effects on the host. […] An unfavorable alteration of the gut virome composition has been implicated in chronic immune disorders, such as in the pathogenesis of IBD. […] Understanding virome–immune system interactions from a broad perspective may be particularly important in intestinal disease because the pathogen recognition receptors (PRRs) are probably simultaneously engaged by different viruses. […] Aberrant regulation of the immune response to infecting viruses may result in chronic inflammation. […] Chronic inflammation is also one of the hallmarks of cancer and promotes all stages of tumorigenesis. […] Although the exact pathway is unknown, chronic inflammation in the colon is suggested to be a link between ulcerative colitis and colorectal cancer.

• #58 Gut virome-colonising Orthohepadnavirus genus is associated with ulcerative colitis pathogenesis and induces intestinal inflammation in vivo | Gut

  https://gut.bmj.com/content/72/10/1838

  HBx was detected in about 45% of patients with UC and found to induce colonic inflammation in mice, while its silencing reverted the colitis phenotype in vivo. […] Notably, the increased diarrhoea and faecal blood observed in HBx-treated mice, along with the mucosal ulceration, led us to propose HBx as a factor that impairs barrier function in the intestinal mucosa, thus promoting gut inflammation. […] Collectively, these results demonstrate that HBx drives colitis in vivo by acting at the level of the epithelial barrier and, in parallel, affects the gut mucosal immune cells, likely not mounting an adequate defence against the invading microorganisms and thus fostering a persistent inflammation unable to self-resolve. […] Conclusively, HBx was shown to impair the functions of epithelial cells by directly binding to intergenic DNA regions, affecting gene expression in epithelial cells that concomitantly acquired a stem-cell-like phenotype and reduced mucin expression, together with the activation of other genes already reported to be involved in UC pathogenesis.

• #59 Gut virome-colonising Orthohepadnavirus genus is associated with ulcerative colitis pathogenesis and induces intestinal inflammation in vivo | Gut

  https://gut.bmj.com/content/72/10/1838

  HBx was detected in about 45% of patients with UC and found to induce colonic inflammation in mice, while its silencing reverted the colitis phenotype in vivo. […] Notably, the increased diarrhoea and faecal blood observed in HBx-treated mice, along with the mucosal ulceration, led us to propose HBx as a factor that impairs barrier function in the intestinal mucosa, thus promoting gut inflammation. […] Collectively, these results demonstrate that HBx drives colitis in vivo by acting at the level of the epithelial barrier and, in parallel, affects the gut mucosal immune cells, likely not mounting an adequate defence against the invading microorganisms and thus fostering a persistent inflammation unable to self-resolve. […] Conclusively, HBx was shown to impair the functions of epithelial cells by directly binding to intergenic DNA regions, affecting gene expression in epithelial cells that concomitantly acquired a stem-cell-like phenotype and reduced mucin expression, together with the activation of other genes already reported to be involved in UC pathogenesis.

• #60 Gut virome-colonising Orthohepadnavirus genus is associated with ulcerative colitis pathogenesis and induces intestinal inflammation in vivo | Gut

  https://gut.bmj.com/content/72/10/1838

  HBx was detected in about 45% of patients with UC and found to induce colonic inflammation in mice, while its silencing reverted the colitis phenotype in vivo. […] Notably, the increased diarrhoea and faecal blood observed in HBx-treated mice, along with the mucosal ulceration, led us to propose HBx as a factor that impairs barrier function in the intestinal mucosa, thus promoting gut inflammation. […] Collectively, these results demonstrate that HBx drives colitis in vivo by acting at the level of the epithelial barrier and, in parallel, affects the gut mucosal immune cells, likely not mounting an adequate defence against the invading microorganisms and thus fostering a persistent inflammation unable to self-resolve. […] Conclusively, HBx was shown to impair the functions of epithelial cells by directly binding to intergenic DNA regions, affecting gene expression in epithelial cells that concomitantly acquired a stem-cell-like phenotype and reduced mucin expression, together with the activation of other genes already reported to be involved in UC pathogenesis.

• #61

  https://journals.lww.com/md-journal/fulltext/2023/09150/pathological_mechanism_and_targeted_drugs_of.44.aspx

  Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with abdominal pain, diarrhea, and mucopurulent stools as the main symptoms. […] The etiology and pathogenesis of ulcerative colitis are reviewed to clarify the targeted drugs of UC in the latest research. […] It is related to the main genetic, environmental, immune and other factors, and explaining its pathogenesis from the NF-B pathway, PI3K/Akt signaling pathway, and JAK/STAT signaling pathway. […] The intestinal mucosal barrier includes a mechanical barrier, an immune barrier, a biological barrier, and a chemical barrier, and the destabilization of any of the intestinal barrier functions will lead to the destruction of the intestinal mucosal tissue, which will cause inflammatory lesions. […] The immune system plays an important role in the development of UC, and disruption of normal immune regulation in the gut or abnormal immune responses are important aspects of UC pathogenesis.

• #62

  https://journals.lww.com/md-journal/fulltext/2023/09150/pathological_mechanism_and_targeted_drugs_of.44.aspx

  The loss of immune tolerance leads to inflammation due to the increased release of antibodies, cytokines, and pro-inflammatory mediators from these effector cells, which stimulate the proliferation of antigen-specific effectors, thereby triggering the adaptive immune system and leading to local and systemic inflammation. […] The NF-B pathway is regulated by tumor necrosis factor (TNF)-, interleukin (IL), etc. […] The expression of intestinal mucosal inflammation was increased in both mouse models of ulcerative colitis and NF-B P-p65 was abundant in colonic tissues, and the loss of regulatory factors on the NF-B signaling pathway leads to pathological changes in the intestinal mucosa of UC. […] The PI3K/Akt signaling pathway is also involved in the regulation and release of inflammatory factors, and it can indirectly activate the transcription factor NF-B through phosphorylated IKK, thus interconnecting with the NF-B pathway to promote enhanced expression and secretion of inflammatory factors, leading to damage of the colonic mucosa.

• #63

  https://journals.lww.com/md-journal/fulltext/2023/09150/pathological_mechanism_and_targeted_drugs_of.44.aspx

  The loss of immune tolerance leads to inflammation due to the increased release of antibodies, cytokines, and pro-inflammatory mediators from these effector cells, which stimulate the proliferation of antigen-specific effectors, thereby triggering the adaptive immune system and leading to local and systemic inflammation. […] The NF-B pathway is regulated by tumor necrosis factor (TNF)-, interleukin (IL), etc. […] The expression of intestinal mucosal inflammation was increased in both mouse models of ulcerative colitis and NF-B P-p65 was abundant in colonic tissues, and the loss of regulatory factors on the NF-B signaling pathway leads to pathological changes in the intestinal mucosa of UC. […] The PI3K/Akt signaling pathway is also involved in the regulation and release of inflammatory factors, and it can indirectly activate the transcription factor NF-B through phosphorylated IKK, thus interconnecting with the NF-B pathway to promote enhanced expression and secretion of inflammatory factors, leading to damage of the colonic mucosa.

• #64 The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis—A Literature Review

  https://www.mdpi.com/2227-9059/11/12/3144

  The gut microbiome plays an essential role in the progression of inflammation. Dysfunction in interactions between gut microbiota and epithelial cells have a significant role in UC pathogenesis. […] The mucus barrier overlying the epithelium is a crucial element in providing an environment for commensal microbes’ colonization. Abnormalities in its structure play a significant role in inflammation onset. […] The mutual impact between the host’s immune system and microbes is possible due to pattern-recognition receptors (PRRs) such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), mannose-binding receptors, complement receptors and C-type lectin receptors (CLRs) expressed on the intestinal epithelial cells and innate immune cells. […] Activation and translocation of NF-κB mediated by MAMPs/PAMPs promote the expression of inflammatory genes but also genes involved in tissue repair, regeneration, and angiogenesis.

• #65 The alleviating effect and mechanism of GLP-1 on ulcerative colitis | Aging

  https://www.aging-us.com/article/204953/text

  GLP-1 also alleviates DSS-induced injury to the intestinal mucosa and dysbiosis of gut microbiota. Altogether, GLP-1 has protection effect on ulcerative colitis. Thus, GLP-1 can be considered as a potential therapeutic candidate for the treatment of UC. […] GLP-1 inhibits the activity of MPO and affected the protein expressions of IL-1, IL-6, and TNF- in ulcerative colitic mice. […] GLP-1 inhibits phosphorylation of NF-B p65 and its upstream kinase AKT consistent with its anti-inflammatory role. […] Our results showed that GLP-1 dephosphorylates P38, ERK1/2 and JNK. GLP-1 treated LPS-induced RAW 264.7 cells showed repression of AKT/NF-B and MAPK signaling pathways. […] This study implies that targeting AKT/NF-B and MAPK signaling pathways can be a way to ameliorate UC inflammatory change.

• #66

  https://journals.lww.com/md-journal/fulltext/2023/09150/pathological_mechanism_and_targeted_drugs_of.44.aspx

  The loss of immune tolerance leads to inflammation due to the increased release of antibodies, cytokines, and pro-inflammatory mediators from these effector cells, which stimulate the proliferation of antigen-specific effectors, thereby triggering the adaptive immune system and leading to local and systemic inflammation. […] The NF-B pathway is regulated by tumor necrosis factor (TNF)-, interleukin (IL), etc. […] The expression of intestinal mucosal inflammation was increased in both mouse models of ulcerative colitis and NF-B P-p65 was abundant in colonic tissues, and the loss of regulatory factors on the NF-B signaling pathway leads to pathological changes in the intestinal mucosa of UC. […] The PI3K/Akt signaling pathway is also involved in the regulation and release of inflammatory factors, and it can indirectly activate the transcription factor NF-B through phosphorylated IKK, thus interconnecting with the NF-B pathway to promote enhanced expression and secretion of inflammatory factors, leading to damage of the colonic mucosa.

• #67 Frontiers | The mechanism of traditional medicine in alleviating ulcerative colitis: regulating intestinal barrier function

  https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1228969/full

  Oxidative stress is a condition caused by an imbalance between the production and elimination of reactive oxygen species (ROS). […] Previous studies have revealed that oxidative stress may disrupt the intestinal epithelial and endothelial tight junctions via regulating protein modification, such as thiol oxidation and phosphorylation. […] NF-κB is a critical transcription factor involved in many biological processes and its overactivation may disrupt the intestinal barrier via various mechanisms and thus affect the development of IBD, including UC. […] The PI3K-AKT pathway is an intracellular signaling pathway critical for many biological processes, such as cell survival, proliferation and angiogenesis. […] Pyroptosis of intestinal epithelial cells plays an important role in barrier dysfunction and gut inflammation.

• #68 The alleviating effect and mechanism of GLP-1 on ulcerative colitis | Aging

  https://www.aging-us.com/article/204953/text

  GLP-1 also alleviates DSS-induced injury to the intestinal mucosa and dysbiosis of gut microbiota. Altogether, GLP-1 has protection effect on ulcerative colitis. Thus, GLP-1 can be considered as a potential therapeutic candidate for the treatment of UC. […] GLP-1 inhibits the activity of MPO and affected the protein expressions of IL-1, IL-6, and TNF- in ulcerative colitic mice. […] GLP-1 inhibits phosphorylation of NF-B p65 and its upstream kinase AKT consistent with its anti-inflammatory role. […] Our results showed that GLP-1 dephosphorylates P38, ERK1/2 and JNK. GLP-1 treated LPS-induced RAW 264.7 cells showed repression of AKT/NF-B and MAPK signaling pathways. […] This study implies that targeting AKT/NF-B and MAPK signaling pathways can be a way to ameliorate UC inflammatory change.

• #69

  https://journals.lww.com/md-journal/fulltext/2023/09150/pathological_mechanism_and_targeted_drugs_of.44.aspx

  The JAK/STAT signaling pathway uses second messengers to transmit extracellular information to the nucleus, influencing target gene expression and cellular responses, coordinating intracellular signaling of more than 50 different ligands, and consisting of 3 parts: tyrosine-associated receptors, JAK/STAT, and the intracellular segment of tyrosine kinase-coupled tyrosine-associated receptors. […] The pathogenesis of UC is still unclear, and it is mainly related to genetic, environmental, immune, and related signaling pathway overexpression and activation, etc. […] The pathogenesis of UC is not caused by a single factor, but by the interaction of multiple factors.

• #70 Ulcerative colitis – Wikipedia

  https://en.wikipedia.org/wiki/Ulcerative_colitis

  After phagocytosing the microbe, the APCs then enter the mesenteric lymph nodes where they present antigens to naive T-cells while also releasing the pro-inflammatory cytokines IL-12 and IL-23 which lead to T cell differentiation into Th1 and Th17 T-cells. […] T-cell mediated inflammation is thought to be driven by the JAK-STAT intracellular T-cell signaling pathway, leading to the transcription, translation and release of inflammatory cytokines.

• #71 Inflammatory bowel disease (IBD) – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/inflammatory-bowel-disease/diagnosis-treatment/drc-20353320

  Anti-inflammatory medicines are often the first step in the treatment of ulcerative colitis, typically for mild to moderate disease. Anti-inflammatories include aminosalicylates, such as mesalamine (Delzicol, Rowasa, others), balsalazide (Colazal) and olsalazine (Dipentum). […] These drugs work in a variety of ways to suppress the immune response that releases inflammation-inducing chemicals into the body. When released, these chemicals can damage the lining of the digestive tract. […] More recently, medicines given by mouth that are known as small molecules have become available for IBD treatment. Janus kinase inhibitors, also called JAK inhibitors, are a type of small molecule medicine that helps reduce inflammation by targeting parts of the immune system that cause inflammation in the intestines. Some JAK inhibitors for IBD include tofacitinib (Xeljanz) and upadacitinib (Rinvoq).

• #72 Frontiers | The mechanism of traditional medicine in alleviating ulcerative colitis: regulating intestinal barrier function

  https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1228969/full

  Oxidative stress is a condition caused by an imbalance between the production and elimination of reactive oxygen species (ROS). […] Previous studies have revealed that oxidative stress may disrupt the intestinal epithelial and endothelial tight junctions via regulating protein modification, such as thiol oxidation and phosphorylation. […] NF-κB is a critical transcription factor involved in many biological processes and its overactivation may disrupt the intestinal barrier via various mechanisms and thus affect the development of IBD, including UC. […] The PI3K-AKT pathway is an intracellular signaling pathway critical for many biological processes, such as cell survival, proliferation and angiogenesis. […] Pyroptosis of intestinal epithelial cells plays an important role in barrier dysfunction and gut inflammation.

• #73 Frontiers | The mechanism of traditional medicine in alleviating ulcerative colitis: regulating intestinal barrier function

  https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1228969/full

  The Notch signaling pathway is a highly conserved pathway that modulates the stem cell fate and phenotype in the intestinal mucosa and thus plays a role in the maintenance of intestinal barrier function. […] HIF-1α is a crucial regulator of oxygen homeostasis. […] RORγT is a transcription factor that controls Th17 cell differentiation and is crucial for the secretion of Th17 effector cytokines. […] The advanced glycation end products-receptor of advanced glycation end products (AGE-RAGE) signaling pathway triggers activation of multiple intracellular pathways.

• #74 The alleviating effect and mechanism of GLP-1 on ulcerative colitis | Aging

  https://www.aging-us.com/article/204953/text

  GLP-1 also alleviates DSS-induced injury to the intestinal mucosa and dysbiosis of gut microbiota. Altogether, GLP-1 has protection effect on ulcerative colitis. Thus, GLP-1 can be considered as a potential therapeutic candidate for the treatment of UC. […] GLP-1 inhibits the activity of MPO and affected the protein expressions of IL-1, IL-6, and TNF- in ulcerative colitic mice. […] GLP-1 inhibits phosphorylation of NF-B p65 and its upstream kinase AKT consistent with its anti-inflammatory role. […] Our results showed that GLP-1 dephosphorylates P38, ERK1/2 and JNK. GLP-1 treated LPS-induced RAW 264.7 cells showed repression of AKT/NF-B and MAPK signaling pathways. […] This study implies that targeting AKT/NF-B and MAPK signaling pathways can be a way to ameliorate UC inflammatory change.

• #75 Hypoxia is a key mechanism for regulating inflammation in ulcerative colitis | Russian Open Medical Journal

  https://romj.org/2020-0101

  Hypoxia plays a key role in both the system and local inflammatory reactions, mainly due to microcirculatory disorders and disseminated intravascular coagulation. […] Severity of any inflammatory diseases, including inflammatory diseases of the gut such as Crohn’s disease (CD) and ulcerative colitis (UC) depends on hypoxia resistance. […] Pathogenesis of the disease is associated with a complex interaction of the genetic factors, the environment, the microbiome and the uncontrolled reaction of the immune system, and the existing treatment methods are not effective enough. […] HIF-1 directly regulates the activation of several protective genes in response to the damage to the epithelial barrier integrity, reduces the production of cytokines and leads to the increase in production of -defensins, that play a key role in antimicrobial immunity.

• #76 Hypoxia is a key mechanism for regulating inflammation in ulcerative colitis | Russian Open Medical Journal

  https://romj.org/2020-0101

  HIF-2 directly regulates the production of some pro-inflammatory cytokines, including tumor necrosis factor-, which leads to HIF-2-induced inflammation. […] Overexpression of both HIF-1 and HIF-2 genes enhances the inflammatory response, which suggests that activation of HIF-1 does not prevent the pro-inflammatory response, induced by HIF-2. […] The role of hypoxia-inducible factors in the development of IBD and UC, as well as their influence on the severity of the inflammatory process, is primarily investigated in experimental models. […] An increase in the severity of DSS colitis was shown in mice with the deficiency of VHL that stabilizes HIF-1 and HIF-2. […] HIF-1 is an anti-inflammatory agent in IBD and it ensures the integrity of the epithelial barrier and antimicrobial immunity by increasing the synthesis of -defensins, while HIF-2 activates pro-inflammatory cytokine production and epithelial proliferation. […] Hypoxia is a key feature of the normal physiology of intestine, and in inflammatory conditions, such as UC, tissue hypoxia may be aggravated.

• #77 Frontiers | The mechanism of traditional medicine in alleviating ulcerative colitis: regulating intestinal barrier function

  https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1228969/full

  Oxidative stress is a condition caused by an imbalance between the production and elimination of reactive oxygen species (ROS). […] Previous studies have revealed that oxidative stress may disrupt the intestinal epithelial and endothelial tight junctions via regulating protein modification, such as thiol oxidation and phosphorylation. […] NF-κB is a critical transcription factor involved in many biological processes and its overactivation may disrupt the intestinal barrier via various mechanisms and thus affect the development of IBD, including UC. […] The PI3K-AKT pathway is an intracellular signaling pathway critical for many biological processes, such as cell survival, proliferation and angiogenesis. […] Pyroptosis of intestinal epithelial cells plays an important role in barrier dysfunction and gut inflammation.

• #78

  https://journals.lww.com/ajg/abstract/2019/10001/682_investigating_the_pathogenesis_of_ulcerative.682.aspx

  Ulcerative colitis (UC) is an inflammatory bowel disease that causes inflammation of the colon and rectum, alongside extra-colonic manifestations. The etiology is unclear but is thought to include such factors as genetic predisposition, immune regulation, microbiome, and environmental triggers. […] Here we use meta-analysis to dissect UC pathogenesis. […] Our analysis identified granulocyte adhesion and diapedesis, TREM1 signaling, and communication between innate and adaptive immune cells as top canonical pathways. […] We noted upregulation of the DUOX/DUOXA2 enzyme system, responsible for generating reactive oxygen species. […] We also found upregulation of calprotectin S100A8, which defines UC severity, and downregulation of the E3 ubiquitin ligase RNF5 responsible for controlling S100A8 expression.

• #79

  https://journals.lww.com/ajg/abstract/2019/10001/682_investigating_the_pathogenesis_of_ulcerative.682.aspx

  Ulcerative colitis (UC) is an inflammatory bowel disease that causes inflammation of the colon and rectum, alongside extra-colonic manifestations. The etiology is unclear but is thought to include such factors as genetic predisposition, immune regulation, microbiome, and environmental triggers. […] Here we use meta-analysis to dissect UC pathogenesis. […] Our analysis identified granulocyte adhesion and diapedesis, TREM1 signaling, and communication between innate and adaptive immune cells as top canonical pathways. […] We noted upregulation of the DUOX/DUOXA2 enzyme system, responsible for generating reactive oxygen species. […] We also found upregulation of calprotectin S100A8, which defines UC severity, and downregulation of the E3 ubiquitin ligase RNF5 responsible for controlling S100A8 expression.

• #80 Exploring the autophagy-related pathogenesis of active ulcerative colitis

  https://www.wjgnet.com/2307-8960/full/v12/i9/1622.htm

  The pathogenesis of ulcerative colitis (UC) is complex, and recent therapeutic advances remain unable to fully alleviate the condition. […] To inform the development of novel UC treatments, bioinformatics was used to explore the autophagy-related pathogenesis associated with the active phase of UC. […] Autophagy is shown to be a key mediator in the pathophysiological processes of UC. […] From a physiological perspective, autophagy plays a critical role in maintaining intestinal balance, regulating interactions between gut microbiota and both the innate and adaptive immune systems, and protecting the host against intestinal pathogens. […] Given the importance of autophagy in preserving intestinal balance and the role of autophagy dysfunction in UC development, identifying autophagy-related disease predictors is essential for the design of new UC treatments.

• #81 Exploring the autophagy-related pathogenesis of active ulcerative colitis

  https://www.wjgnet.com/2307-8960/full/v12/i9/1622.htm

  The pathogenesis of ulcerative colitis (UC) is complex, and recent therapeutic advances remain unable to fully alleviate the condition. […] To inform the development of novel UC treatments, bioinformatics was used to explore the autophagy-related pathogenesis associated with the active phase of UC. […] Autophagy is shown to be a key mediator in the pathophysiological processes of UC. […] From a physiological perspective, autophagy plays a critical role in maintaining intestinal balance, regulating interactions between gut microbiota and both the innate and adaptive immune systems, and protecting the host against intestinal pathogens. […] Given the importance of autophagy in preserving intestinal balance and the role of autophagy dysfunction in UC development, identifying autophagy-related disease predictors is essential for the design of new UC treatments.

• #82 Exploring the autophagy-related pathogenesis of active ulcerative colitis

  https://www.wjgnet.com/2307-8960/full/v12/i9/1622.htm

  The current study uses bioinformatics to define gene expression patterns associated with the autophagy-related pathogenesis of active UC. […] Autophagy is closely related to the active phase of UC and the potential targets obtained from the analysis in this study may provide new insight into the treatment of active UC patients. […] HSPA5, CASP1, SERPINA1, CX3CL1, and BAG3 were identified as core autophagy-related targets in active UC, all of which were upregulated during the disease. […] These findings provide valuable insight into the role of autophagy in UC pathogenesis and have potential implications for the development of novel targeted therapies.

• #83 Exploring the autophagy-related pathogenesis of active ulcerative colitis

  https://www.wjgnet.com/2307-8960/full/v12/i9/1622.htm

  The current study uses bioinformatics to define gene expression patterns associated with the autophagy-related pathogenesis of active UC. […] Autophagy is closely related to the active phase of UC and the potential targets obtained from the analysis in this study may provide new insight into the treatment of active UC patients. […] HSPA5, CASP1, SERPINA1, CX3CL1, and BAG3 were identified as core autophagy-related targets in active UC, all of which were upregulated during the disease. […] These findings provide valuable insight into the role of autophagy in UC pathogenesis and have potential implications for the development of novel targeted therapies.

• #84 Ulcerative colitis | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-020-0205-x

  Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown aetiology affecting the colon and rectum. Multiple factors, such as genetic background, environmental and luminal factors, and mucosal immune dysregulation, have been suggested to contribute to UC pathogenesis. […] An improved understanding of the mechanisms underlying UC has led to the emergence of new treatments. […] However, delineating the aetiology of UC is necessary to ultimately achieve disease cure.

• #85 Cytokines in the Pathogenesis of Ulcerative Colitis – Giorgos Bamias – Discovery Medicine

  https://www.discoverymedicine.com/Giorgos-Bamias/2011/05/23/cytokines-in-the-pathogenesis-of-ulcerative-colitis/

  Based on the studies mentioned above, a pathogenetic scheme has been proposed for the involvement of IL-13 in UC pathogenesis. According to this theory, unidentified stimuli, most probably commensal flora-derived microbial products, stimulate atypical NKT cells to produce IL-13 in the colonic mucosa. The downstream effects culminate to epithelial injury as a result of the cytotoxic activity of NKT cells on epithelial cells, the IL-13 induced apoptosis of colonocytes, and the overall disruption of tight junctions. This pathogenetic scheme fits with the pathological phenotype of injury in UC that consists of extensive destruction of the colonic epithelial layer. […] A proof of principle for this proposed pathogenetic role of IL-13 in UC-associated intestinal inflammation is provided by a recent study that reported a positive correlation between effective anti-inflammatory treatment and mucosal and/or systemic levels of the cytokine.

• #86 Cytokines in the Pathogenesis of Ulcerative Colitis – Giorgos Bamias – Discovery Medicine

  https://www.discoverymedicine.com/Giorgos-Bamias/2011/05/23/cytokines-in-the-pathogenesis-of-ulcerative-colitis/

  Further support for the role of IL-13 and its receptor IL-13R2 in UC is provided by a recent study that utilized microarray technology to identify molecular predictors of response to treatment with infliximab. […] TL1A (designated as TNFSF15) has the ability to bind to two receptors of the TNF receptor superfamily (TNFRSF), which display opposing functions. In particular, DR3 (death domain containing receptor 3, TNFRSF25) is a functional receptor and TL1A/DR3 association provides co-stimulatory signals for activated lymphocytes, leading to cell proliferation and cytokine secretion and amplifying pro-inflammatory pathways. […] Several recent publications have clearly demonstrated that the system of TL1A/DR3/DcR3 is upregulated in IBD. […] Recent studies have shown that, in addition to TL1A and DR3, the decoy receptor DcR3 is also upregulated in active UC.

• #87 Cytokines in the Pathogenesis of Ulcerative Colitis – Giorgos Bamias – Discovery Medicine

  https://www.discoverymedicine.com/Giorgos-Bamias/2011/05/23/cytokines-in-the-pathogenesis-of-ulcerative-colitis/

  Further support for the role of IL-13 and its receptor IL-13R2 in UC is provided by a recent study that utilized microarray technology to identify molecular predictors of response to treatment with infliximab. […] TL1A (designated as TNFSF15) has the ability to bind to two receptors of the TNF receptor superfamily (TNFRSF), which display opposing functions. In particular, DR3 (death domain containing receptor 3, TNFRSF25) is a functional receptor and TL1A/DR3 association provides co-stimulatory signals for activated lymphocytes, leading to cell proliferation and cytokine secretion and amplifying pro-inflammatory pathways. […] Several recent publications have clearly demonstrated that the system of TL1A/DR3/DcR3 is upregulated in IBD. […] Recent studies have shown that, in addition to TL1A and DR3, the decoy receptor DcR3 is also upregulated in active UC.

• #88 Cytokines in the Pathogenesis of Ulcerative Colitis – Giorgos Bamias – Discovery Medicine

  https://www.discoverymedicine.com/Giorgos-Bamias/2011/05/23/cytokines-in-the-pathogenesis-of-ulcerative-colitis/

  Taken together these results suggest a role for soluble DcR3 as a marker of disease activity in UC. […] IL-33 (formerly known as IL1F11) is the latest identified member of the IL-1 family of cytokines. […] The expression of IL-33 mRNA was significantly elevated in biopsy specimens from inflamed colonic areas in patients with active UC as compared to healthy controls, whereas expression in biopsies from patients with inactive disease differed between studies. […] Taken together, these expression studies clearly show that, during active intestinal inflammation, IL-33 and ST2 localize in epithelial cells and lamina propia immunocytes, respectively, indicating an active participation in the epithelial-immune cell crosstalk that takes place in IBD. […] The great progress that took place in recent years in the field of mucosal immunology has resulted in an abundance of incoming information regarding the immunopathogenesis of UC.

• #89 Cytokines in the Pathogenesis of Ulcerative Colitis – Giorgos Bamias – Discovery Medicine

  https://www.discoverymedicine.com/Giorgos-Bamias/2011/05/23/cytokines-in-the-pathogenesis-of-ulcerative-colitis/

  Taken together these results suggest a role for soluble DcR3 as a marker of disease activity in UC. […] IL-33 (formerly known as IL1F11) is the latest identified member of the IL-1 family of cytokines. […] The expression of IL-33 mRNA was significantly elevated in biopsy specimens from inflamed colonic areas in patients with active UC as compared to healthy controls, whereas expression in biopsies from patients with inactive disease differed between studies. […] Taken together, these expression studies clearly show that, during active intestinal inflammation, IL-33 and ST2 localize in epithelial cells and lamina propia immunocytes, respectively, indicating an active participation in the epithelial-immune cell crosstalk that takes place in IBD. […] The great progress that took place in recent years in the field of mucosal immunology has resulted in an abundance of incoming information regarding the immunopathogenesis of UC.

• #90 Inflammatory bowel disease (IBD) – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/inflammatory-bowel-disease/diagnosis-treatment/drc-20353320

  Anti-inflammatory medicines are often the first step in the treatment of ulcerative colitis, typically for mild to moderate disease. Anti-inflammatories include aminosalicylates, such as mesalamine (Delzicol, Rowasa, others), balsalazide (Colazal) and olsalazine (Dipentum). […] These drugs work in a variety of ways to suppress the immune response that releases inflammation-inducing chemicals into the body. When released, these chemicals can damage the lining of the digestive tract. […] More recently, medicines given by mouth that are known as small molecules have become available for IBD treatment. Janus kinase inhibitors, also called JAK inhibitors, are a type of small molecule medicine that helps reduce inflammation by targeting parts of the immune system that cause inflammation in the intestines. Some JAK inhibitors for IBD include tofacitinib (Xeljanz) and upadacitinib (Rinvoq).

• #91 Frontiers | The mechanism of traditional medicine in alleviating ulcerative colitis: regulating intestinal barrier function

  https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1228969/full

  Oxidative stress is a condition caused by an imbalance between the production and elimination of reactive oxygen species (ROS). […] Previous studies have revealed that oxidative stress may disrupt the intestinal epithelial and endothelial tight junctions via regulating protein modification, such as thiol oxidation and phosphorylation. […] NF-κB is a critical transcription factor involved in many biological processes and its overactivation may disrupt the intestinal barrier via various mechanisms and thus affect the development of IBD, including UC. […] The PI3K-AKT pathway is an intracellular signaling pathway critical for many biological processes, such as cell survival, proliferation and angiogenesis. […] Pyroptosis of intestinal epithelial cells plays an important role in barrier dysfunction and gut inflammation.

• #92 Frontiers | The mechanism of traditional medicine in alleviating ulcerative colitis: regulating intestinal barrier function

  https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1228969/full

  The Notch signaling pathway is a highly conserved pathway that modulates the stem cell fate and phenotype in the intestinal mucosa and thus plays a role in the maintenance of intestinal barrier function. […] HIF-1α is a crucial regulator of oxygen homeostasis. […] RORγT is a transcription factor that controls Th17 cell differentiation and is crucial for the secretion of Th17 effector cytokines. […] The advanced glycation end products-receptor of advanced glycation end products (AGE-RAGE) signaling pathway triggers activation of multiple intracellular pathways.

• #93 Hypoxia is a key mechanism for regulating inflammation in ulcerative colitis | Russian Open Medical Journal

  https://romj.org/2020-0101

  Hypoxia plays a key role in both the system and local inflammatory reactions, mainly due to microcirculatory disorders and disseminated intravascular coagulation. […] Severity of any inflammatory diseases, including inflammatory diseases of the gut such as Crohn’s disease (CD) and ulcerative colitis (UC) depends on hypoxia resistance. […] Pathogenesis of the disease is associated with a complex interaction of the genetic factors, the environment, the microbiome and the uncontrolled reaction of the immune system, and the existing treatment methods are not effective enough. […] HIF-1 directly regulates the activation of several protective genes in response to the damage to the epithelial barrier integrity, reduces the production of cytokines and leads to the increase in production of -defensins, that play a key role in antimicrobial immunity.

• #94 Hypoxia is a key mechanism for regulating inflammation in ulcerative colitis | Russian Open Medical Journal

  https://romj.org/2020-0101

  HIF-2 directly regulates the production of some pro-inflammatory cytokines, including tumor necrosis factor-, which leads to HIF-2-induced inflammation. […] Overexpression of both HIF-1 and HIF-2 genes enhances the inflammatory response, which suggests that activation of HIF-1 does not prevent the pro-inflammatory response, induced by HIF-2. […] The role of hypoxia-inducible factors in the development of IBD and UC, as well as their influence on the severity of the inflammatory process, is primarily investigated in experimental models. […] An increase in the severity of DSS colitis was shown in mice with the deficiency of VHL that stabilizes HIF-1 and HIF-2. […] HIF-1 is an anti-inflammatory agent in IBD and it ensures the integrity of the epithelial barrier and antimicrobial immunity by increasing the synthesis of -defensins, while HIF-2 activates pro-inflammatory cytokine production and epithelial proliferation. […] Hypoxia is a key feature of the normal physiology of intestine, and in inflammatory conditions, such as UC, tissue hypoxia may be aggravated.

• #95

  https://journals.lww.com/ajg/abstract/2019/10001/682_investigating_the_pathogenesis_of_ulcerative.682.aspx

  Impaired epithelial integrity was suggested by upregulation of matrix metalloproteinases MMP1 and MMP3 and down regulation of claudin 8. […] Furthermore, downregulation of aquaporin 8 and guanylin suggests loss of absorption. […] Upregulation of the amino acid transporter SLC6A14 and aldolase B may represent a compensation for loss of absorptive function. […] UC pathogenesis represents a multifactorial disease process that remains elusive. […] Here we suggest several mechanisms that may underpin UC development and susceptibility. […] Our results also demonstrate the parts that DUOX/DUOXA2 system and loss of epithelial and metabolic integrity have in UC. […] Lastly, miRNAs have an emerging role in UC and mimic therapy of the downregulated miRNAs we identified may prove efficacious.

• #96 CD131 Contributes to Ulcerative Colitis Pathogenesis by Promoting Macrophage Infiltration

  https://elifesciences.org/reviewed-preprints/102637v1

  CD131 may have promoted the chemotaxis of macrophages and T cells into the colon through CCL4. […] The present study provides a novel way to the understanding of the mechanisms of GM-CSF and IL-3 effects in the intestine, which will benefit the development of therapeutic approaches. […] CD131 was associated with the endoscopic and pathological severity of intestinal inflammation, as well as macrophage and T cell infiltration in the colon during ulcerative colitis, reflecting its clinical significance.

• #97 Understanding a Novel Mechanism of Action in Ulcerative Colitis

  https://www.gastroendonews.com/Multimedia/Article/10-24/ulcerative-colitis-mechanism-of-action-microRNA-immune-response-inflammatory-bowel-disease-IBD-clinical-trial/75194

  In this webinar, gastroenterologist Parambir S. Dulai, MD, discusses the clinical profile of obefazimod, an investigational once-daily oral small molecule being studied for the treatment of moderately to severely active ulcerative colitis and how its novel mechanism of action enhances the expression of a single microRNA, miR-124, a natural regulator of the immune response. […] its novel mechanism of action enhances the expression of a single microRNA, miR-124, a natural regulator of the immune response.

• #98 The alleviating effect and mechanism of GLP-1 on ulcerative colitis | Aging

  https://www.aging-us.com/article/204953/text

  Ulcerative Colitis (UC) is a major type of chronic inflammatory bowel disease of the colonic mucosa and exhibits progressive morbidity. […] The pathogenic mechanisms of UC have attracted the attention of the scientific world. Apart from genetic susceptibility, factors such as inflammatory response, dysbiosis of the intestinal microbiome, and dysfunction of the intestinal barrier promote the etiopathogenesis of UC. […] The intestinal mucosal surface acts as a barrier to maintain homeostasis between immune cells and the gut microbiome. In UC, a disrupted intestinal barrier leads to the translocation of the gut microbiota into the intestinal tissue resulting in inflammation. […] The effect of GLP-1 was studied by using a dextran sulfate sodium (DSS)-induced colitic mice and lipopolysaccharide (LPS) treated RAW264.7 cells (macrophage cell line) under in vivo and in vitro conditions, respectively. Our results indicate that GLP-1 significantly relieves ulcerative colitis as it represses the production of proinflammatory mediators. In addition, GLP-1 blocks the activation of the protein kinase B (AKT)/nuclear factor-B (NF-B), and mitogen-activated protein kinase (MAPK) signaling pathways.

• #99 The alleviating effect and mechanism of GLP-1 on ulcerative colitis | Aging

  https://www.aging-us.com/article/204953/text

  Ulcerative Colitis (UC) is a major type of chronic inflammatory bowel disease of the colonic mucosa and exhibits progressive morbidity. […] The pathogenic mechanisms of UC have attracted the attention of the scientific world. Apart from genetic susceptibility, factors such as inflammatory response, dysbiosis of the intestinal microbiome, and dysfunction of the intestinal barrier promote the etiopathogenesis of UC. […] The intestinal mucosal surface acts as a barrier to maintain homeostasis between immune cells and the gut microbiome. In UC, a disrupted intestinal barrier leads to the translocation of the gut microbiota into the intestinal tissue resulting in inflammation. […] The effect of GLP-1 was studied by using a dextran sulfate sodium (DSS)-induced colitic mice and lipopolysaccharide (LPS) treated RAW264.7 cells (macrophage cell line) under in vivo and in vitro conditions, respectively. Our results indicate that GLP-1 significantly relieves ulcerative colitis as it represses the production of proinflammatory mediators. In addition, GLP-1 blocks the activation of the protein kinase B (AKT)/nuclear factor-B (NF-B), and mitogen-activated protein kinase (MAPK) signaling pathways.

• #100 Ulcerative colitis: understanding its cellular pathology could provide insights into novel therapies | Journal of Inflammation | Full Text

  https://journal-inflammation.biomedcentral.com/articles/10.1186/s12950-020-00246-4

  To dissect the molecular basis of UC, it is necessary to have thorough knowledge of the cellular populations that constitute the large intestine. […] Correct functioning of specialized intestinal epithelial cells is essential to maintain intestinal homeostasis and its dysfunction plays a central role in the pathogenesis of several diseases, including UC. […] UC is a multifactorial disorder; genetic predisposition, epithelial barrier defects, dysregulated immune responses and environmental factors play a role in its pathogenesis. […] Although the exact aetiology of UC remains elusive, the commensal luminal flora is known to trigger an inappropriate and overactive mucosal immune response in genetically susceptible individuals, causing intestinal tissue damage. […] Autoantibodies in the mucosa of the large intestine may play a part in the pathogenesis of this disease.

• #101 Pathogenesis, Diagnosis, and Treatment of Ulcerative Colitis | Frontiers Research Topic

  https://www.frontiersin.org/research-topics/42033/pathogenesis-diagnosis-and-treatment-of-ulcerative-colitis

  Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology that is a risk factor for colorectal cancer. […] Multiple factors contribute to UC pathogenesis, including genetic background, environmental and luminal factors, and mucosal immune dysregulation. […] Thus, an improved understanding of the mechanisms underlying UC, the development of novel drugs, and the improvement of the treatment strategy is needed. […] Advances in the understanding of disease pathogenesis in ulcerative colitis. […] Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment.

• #102 Ulcerative colitis | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-020-0205-x

  Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown aetiology affecting the colon and rectum. Multiple factors, such as genetic background, environmental and luminal factors, and mucosal immune dysregulation, have been suggested to contribute to UC pathogenesis. […] An improved understanding of the mechanisms underlying UC has led to the emergence of new treatments. […] However, delineating the aetiology of UC is necessary to ultimately achieve disease cure.

• #103 Pathogenesis, Diagnosis, and Treatment of Ulcerative Colitis | Frontiers Research Topic

  https://www.frontiersin.org/research-topics/42033/pathogenesis-diagnosis-and-treatment-of-ulcerative-colitis

  Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology that is a risk factor for colorectal cancer. […] Multiple factors contribute to UC pathogenesis, including genetic background, environmental and luminal factors, and mucosal immune dysregulation. […] Thus, an improved understanding of the mechanisms underlying UC, the development of novel drugs, and the improvement of the treatment strategy is needed. […] Advances in the understanding of disease pathogenesis in ulcerative colitis. […] Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment.

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