• 7α-dehydroxylating Bacteria
• Bile Acids
• Intestinal Mucosal Healing
• Ulcerative Colitis

• Animals
• Bile Acids and Salts/metabolism
• Intestinal Mucosa/pathology
• Colon/pathology
• Humans
• Mice
• Clostridium/metabolism
• Mice, Inbred C57BL
• Disease Models, Animal
• Male
• Wound Healing
• Colitis/therapy
• Colitis/chemically induced
• Colitis/pathology

• 310030_189178 Swiss National Science Foundation
• CRSII5_180317/1 Swiss National Science Foundation
• CRSII5_180317/1 Swiss National Science Foundation
• CRSII5_180317/1 Swiss National Science Foundation

• Rhodnius prolixus
• Toxoplasma gondii
• Cytokines
• Inflammatory bowel diseases
• Saliva
• Triatomines

• 309364/2022-1 Conselho Nacional de Desenvolvimento Científico e Tecnológico
• Fundanção de Amparo a Pesquisa de Minas Gerais

• Astragaloside IV (AS-IV)
• Mucosal barrier
• Network pharmacology
• PI3K/AKT
• Ulcerative colitis (UC)

• Animals
• Humans
• Male
• Mice
• Caco-2 Cells
• Colitis, Ulcerative/drug therapy
• Colitis, Ulcerative/pathology
• Colitis, Ulcerative/metabolism
• Intestinal Mucosa/drug effects
• Intestinal Mucosa/pathology
• Intestinal Mucosa/metabolism
• Mice, Inbred C57BL
• Phosphatidylinositol 3-Kinases/metabolism
• Proto-Oncogene Proteins c-akt/metabolism
• Saponins/pharmacology
• Saponins/therapeutic use
• Signal Transduction/drug effects
• Triterpenes/pharmacology
• Triterpenes/therapeutic use

• Grant No.: 82270563 National Natural Science Foundation of China
• Grant No.:82000522 National Natural Science Foundation of China
• Grant No.: GK202205010 Fundamental Research Funds for the Central Universities
• Grant No.: 2021-01-ZZ-017 Shaanxi Administration of Traditional Chinese Medicine

• barrier integrity
• epithelial homeostasis
• immune signaling
• pathogen detection
• tissue repair

• Homeostasis
• Humans
• Intestinal Mucosa/microbiology
• Intestinal Mucosa/immunology
• Intestinal Mucosa/metabolism
• Animals
• Immunity, Innate
• Respiratory Mucosa/microbiology
• Respiratory Mucosa/immunology
• Epithelial Cells/microbiology
• Signal Transduction
• Adaptive Immunity
• Macrophages/immunology
• Macrophages/microbiology
• Host-Pathogen Interactions

• DKK-1 inhibitor
• Inflammatory bowel disease
• WAY-262611
• Wnt/β-catenin

• Mice
• Animals
• beta Catenin/metabolism
• Inflammatory Bowel Diseases/drug therapy
• Inflammatory Bowel Diseases/genetics
• Wnt Signaling Pathway
• Colorectal Neoplasms
• Rodent Diseases
• Naphthalenes
• Piperidines
• Pyrimidines

• Inflammatory bowel disease
• RANKL/RANK/OPG pathway
• Wnt pathways
• bone loss

• Frizzled 7
• Goblet/Paneth cells
• Inflammation
• Intestinal epithelium
• Tumorigenesis

• Animals
• Mice
• Cell Differentiation
• Enterocolitis/metabolism
• Goblet Cells/metabolism
• Homeostasis
• Intestinal Mucosa/metabolism
• Intestines
• Paneth Cells
• Wnt Signaling Pathway

• Ministry of Education
• MOHW108-TDU-B-212-124014 Ministry of Health and Welfare
• MOST-110-2320-B-038-070 Ministry of Science and Technology, Taiwan
• DP2-109-21121-01-O-02-04 Taipei Medical University
• MOST-108-2321-B-038-003 Ministry of Science and Technology

• immunosurveillance
• immunotherapy

• Drosophila melanogaster
• drug discovery
• inflammatory bowel disease
• molecular pathways
• natural products

• Acute ileitis
• Algorithmic approach
• Chronic ileitis
• Crypt architecture
• Histological patterns
• Ileal biopsy interpretation

• Computational model
• Crohn’s disease
• Mucosal healing

• Biomaterials
• Bone healing
• Cell-sheets/ -aggregates
• Cytotherapy
• Exosomes
• Extracellular matrix
• Mesenchymal stem cells
• Regenerative medicine

This study aimed to determine whether Danggui Buxue decoction (DGBX) can improve inflammatory bowel disease (IBD) by regulating immunity and promoting intestinal mucosal repair.

Dextran sulfate sodium (DSS) was used to induce the IBD model. Drugs (DGBX or saline) were administered to mice, which were randomly divided into three groups (control, model, and experimental groups). Hematoxylin and eosin staining of intestinal tissues was conducted to observe for morphological changes. Changes in cytokines and immune cells in the intestinal tissues were detected by enzyme-linked immunosorbent assay and flow cytometry. Immunofluorescence techniques were used to assess the status of the intestinal mucosal repair.

This study found that treatment with DGBX can effectively improve the inflammatory state and pathological structure of the IBD model. DGBX not only can significantly change the composition of intestinal mucosal immune cells and promote the regression of inflammation but also significantly increase the proliferation of intestinal epithelial cells and promote the rapid repair of intestinal mucosal barrier injury compared with the model group (p < 0.05).

Taking these results, DGBX shows promising protective effects on IBD by regulating immunity and promoting intestinal mucosal repair.

WNT/β-catenin signaling pathways play a pivotal role in the human immune defense against infections and in chronic inflammatory conditions as psoriasis. Wnt gene alterations are linked to known comorbidities of psoriasis as obesity, diabetes and Crohn’s disease. The objective of this study was to investigate WNT7B, WNT10B, WNT16 and TCF7L2 gene and protein expression in lesional and non-lesional skin and in the peripheral blood of patients with chronic plaque psoriasis compared with healthy individuals. To investigate the effect of narrowband UVB radiation, expression of these genes were analyzed before and after narrowband UVB treatment. Associations between single nucleotide polymorphisms for WNT7B, WNT10B, WNT16 and TCF7L2 genes and psoriasis were tested. Our results show significantly decreased WNT7B, WNT10B and TCF7L2 gene expression in lesional skin compared with non-lesional skin and healthy controls. Narrowband UVB treatment significantly increased expression of these genes in lesional skin. Immunohistochemistry shows increased WNT16 expression in lesional skin. No significant differences in allele or genotype frequencies for Wnt or TCF7L2 gene polymorphisms were found between patient and control group. This study shows for the first time significant UVB induced upregulation of WNT7B, WNT10B and TCF7L2 in patients with psoriasis and suggests a potential role of these genes in psoriasis pathogenesis.

• Gene expression
• Inflammation
• Single nucleotide polymorphisms
• WNT proteins
• WNT/β-catenin signaling

• Animals
• Homeostasis
• Humans
• Immune System Diseases/immunology
• Immune System Diseases/pathology
• Stem Cell Niche/immunology
• Stem Cells/immunology

• F31 AR068920 NIAMS NIH HHS
• R01 AR031737 NIAMS NIH HHS
• R01 AR050452 NIAMS NIH HHS
• Howard Hughes Medical Institute

• IEC
• ISC
• immunity
• insulin-like growth factor 1
• microbiota

• Animals
• Bacterial Translocation/genetics
• Cell Lineage
• Cell Proliferation/genetics
• Energy Metabolism/genetics
• Epithelial Cells/cytology
• Epithelial Cells/physiology
• Gastrointestinal Microbiome/genetics
• Gene Expression Profiling
• Gene Expression Regulation
• Homeostasis
• Immunity, Mucosal/genetics
• Immunity, Mucosal/immunology
• Insulin-Like Growth Factor I/genetics
• Insulin-Like Growth Factor I/immunology
• Insulin-Like Growth Factor I/physiology
• Intestinal Absorption/genetics
• Intestinal Mucosa/cytology
• Intestinal Mucosa/immunology
• Liver/microbiology
• Lymph Nodes/microbiology
• Lymphocytes/cytology
• Mesentery
• Mice
• Mice, Knockout
• Nutrients/metabolism
• Proteins/metabolism
• RNA, Ribosomal, 16S
• Radiation Tolerance/genetics
• Regeneration/genetics
• Stem Cells/cytology

• CREB
• inflammatory bowel disease
• intestinal epithelial barrier
• intracellular calcium signaling

• ADAM10
• Cell lineage specification
• Intestinal stem cells
• Notch

• ADAM10 Protein/genetics
• ADAM10 Protein/metabolism
• Amyloid Precursor Protein Secretases/genetics
• Amyloid Precursor Protein Secretases/metabolism
• Carcinogenesis/genetics
• Cell Membrane/genetics
• Humans
• Inflammation/genetics
• Inflammation/pathology
• Membrane Proteins/genetics
• Membrane Proteins/metabolism
• Neoplasms/genetics
• Neoplasms/pathology
• Proteolysis

• R01 DK093697 NIDDK NIH HHS

In mammalian intestines, Notch signaling plays a critical role in mediating cell fate decisions; it promotes the absorptive (or enterocyte) cell fate, while concomitantly inhibiting the secretory cell fate (i.e. goblet, Paneth and enteroendocrine cells). We recently reported that intestinal-specific Kaiso overexpressing mice (Kaiso^Tg) exhibited chronic intestinal inflammation and had increased numbers of all three secretory cell types, hinting that Kaiso might regulate Notch signaling in the gut. However, Kaiso’s precise role in Notch signaling and whether the Kaiso^Tg secretory cell fate phenotype was linked to Kaiso-induced inflammation had yet to be elucidated.

Intestines from 3-month old Non-transgenic and Kaiso^Tg mice were “Swiss” rolled and analysed for the expression of Notch1, Dll-1, Jagged-1, and secretory cell markers by immunohistochemistry and immunofluorescence. To evaluate inflammation, morphological analyses and myeloperoxidase assays were performed on intestines from 3-month old Kaiso^Tg and control mice. Notch1, Dll-1 and Jagged-1 expression were also assessed in stable Kaiso-depleted colon cancer cells and isolated intestinal epithelial cells using real time PCR and western blotting. To assess Kaiso binding to the DLL1, JAG1 and NOTCH1 promoter regions, chromatin immunoprecipitation was performed on three colon cancer cell lines.

Here we demonstrate that Kaiso promotes secretory cell hyperplasia independently of Kaiso-induced inflammation. Moreover, Kaiso regulates several components of the Notch signaling pathway in intestinal cells, namely, Dll-1, Jagged-1 and Notch1. Notably, we found that in Kaiso^Tg mice intestines, Notch1 and Dll-1 expression are significantly reduced while Jagged-1 expression is increased. Chromatin immunoprecipitation experiments revealed that Kaiso associates with the DLL1 and JAG1 promoter regions in a methylation-dependent manner in colon carcinoma cell lines, suggesting that these Notch ligands are putative Kaiso target genes.

Here, we provide evidence that Kaiso’s effects on intestinal secretory cell fates precede the development of intestinal inflammation in Kaiso^Tg mice. We also demonstrate that Kaiso inhibits the expression of Dll-1, which likely contributes to the secretory cell phenotype observed in our transgenic mice. In contrast, Kaiso promotes Jagged-1 expression, which may have implications in Notch-mediated colon cancer progression.

The online version of this article (doi:10.1186/s12964-017-0178-x) contains supplementary material, which is available to authorized users.

• Dll-1
• Intestinal cell fates
• Intestinal homeostasis
• Jagged-1
• Kaiso
• Notch

• Paneth cell
• intestinal epithelium
• intestinal microbiota
• intestinal stem cells
• niche

Inflammatory bowel disease (IBD) includes a set of pathologies that result from a deregulated immune response that may affect any portion of the gastrointestinal tract. The most prevalent and defined forms of IBD are Crohn’s disease and ulcerative colitis. Although the etiology of IBD is not well defined, it has been suggested that environmental and genetic factors contribute to disease development and that the interaction between these two factors can trigger the pathology. Diet, medication use, vitamin D status, smoking, and bacterial infections have been proposed to influence or contribute to the onset or development of the disease in susceptible individuals. The infection with pathogenic bacteria is a key factor that can influence the development and severity of this disease. Here, we present a comprehensive review of studies performed in human and mice susceptible to IBD, which supports the notion that infection with bacterial pathogens, such as Salmonella, could promote the onset of IBD due to permanent changes in the intestinal microbiota, disruption of the epithelial barrier and alterations of the intestinal immune response after infection.

• Crohn’s disease
• Salmonella enterica serovar Typhimurium
• gut microbiota
• inflammatory bowel disease
• innate immune response
• ulcerative colitis
• virulence factors

There is consensus that inflammatory bowel diseases (IBDs) are the result of “dysregulated” immune reactivity towards commensal microorganisms in the intestine. This gut microbiome is clearly altered in IBD, but its primary or secondary role is still debated. The focus has shifted from adaptive to innate immunity, with its multitude of receptor molecules (Toll-like and NOD receptors) and antibacterial effector molecules (defensins, cathelicidin, and others). The latter appear to be at least partly deficient at different intestinal locations. Host genetics also support the notion that microbe–host interaction at the mucosa is the prime site of pathogenesis. In contrast, even the latest therapeutic antibodies are directed against secondary targets like cytokines and integrins identified decades ago. These so-called “biologicals” have disappointing long-term results, with the majority of patients not achieving remission in the long run. A promising approach is the development of novel drugs like defensin-derived molecules that substitute for the missing endogenous antibacterials.

• Crohn's disease
• IBD treatment
• inflammatory bowel disease

• Biomarkers
• cancer stem cells
• cholangiocarcinoma
• chronic inflammation
• tumor microenvironment

The Wnt signaling pathway plays a key role in many biological aspects, such as cellular proliferation, tissue regeneration, embryonic development, and other systemic effects. Under a physiological condition, it is tightly controlled at different layers and arrays, and a dysregulated activation of this signaling has been implicated into the pathogenesis of various human disorders, including autoimmune diseases. Despite the fact that therapeutic interventions are available for ameliorating disease manifestations, there is no curative therapy currently available for autoimmune disorders. Increasing lines of evidence have suggested a crucial role of Wnt signaling during the pathogenesis of many autoimmune diseases; in addition, some of microRNAs (miRNAs), a class of small, noncoding RNA molecules capable of transcriptionally regulating gene expression, have also recently been demonstrated to possess both physiological and pathological roles in autoimmune diseases by regulating the Wnt signaling pathway. This review summarizes currently our understanding of the pathogenic roles of Wnt signaling in several major autoimmune disorders and miRNAs, those targeting Wnt signaling in autoimmune diseases, with a focus on the implication of the Wnt signaling as potential biomarkers and therapeutic targets in immune diseases, as well as miRNA-mediated regulation of Wnt signaling activation in the development of autoimmune diseases.

AIM: To observe the effect of traditional Chinese compound medicine Jianpi Bushen Qingchang Huashi Decoction combined with bone mesenchymal stem cells (BMSCs) in the repair of the intestinal mucosa of rats with ulcerative colitis.

METHODS: Rats were divided into five groups: a normal group, a model group, a BMSCs group, an intervened BMSCs group and a combination group. The rats of the normal and model groups received an intravenous injection of normal saline separately through the tail vein. The BMSCs group received an intravenous injection of BMSCs (1 × 10⁶/mL) through the tail vein. The intervened BMSCs group and combination group received BMSCs (1 × 10⁶/mL) intervened by decoction in vitro, and the combination group additionally received the oral decoction for 10 d. Five rats were killed on the 5^th and 10^th day after the transplantation, respectively. The mRNA and protein expression of Muc2 was detected by real-time PCR and Western blot, respectively. Expression of Math1 and KLF-4 was assayed by Western blot.

RESULTS: The number of goblet cells was increased in each BMSCs transplantation group. The mRNA expression of Muc2 significantly increased in each treatment group relative to the model group, and the increase was more significant in the combination group than in the intervened BMSCs and BMSCs groups. As time increased, the therapeutic effect was more obvious. On the 10^th day of treatment, compared with the normal group, Muc2, Math1 and KLF-4 protein expression was significantly decreased in the model group, while the expression of these proteins was higher in the treatment groups, with the combination group increasing most obviously.

CONCLUSION: Transplantation of BMSCs combined with traditional compound Chinese medicine could improve the mRNA and protein expression of Muc2 in UC rats, reduce inflammation and repair intestinal barrier, which may be related to the Math1 and KLF-4 factors.

• Ulcerative colitis
• Jianpi Bushen Qingchang Huashi
• Mesenchymal stem cells
• Mucus barrier

• ADAM10
• ADAM17
• EGFR
• Notch
• TNFα
• intestinal stem cells

• Crohn’s disease
• IBD
• Mobilization
• Stem cells
• Ulcerative colitis

Inflammatory Bowel Disease (IBD) represents a group of idiopathic disorders characterized by chronic or recurring inflammation of the gastrointestinal tract. While the exact etiology of disease is unknown, IBD is recognized to be a complex, multifactorial disease that results from an intricate interplay of genetic predisposition, an altered immune response, changes in the intestinal microbiota, and environmental factors. Together, these contribute to a destruction of the intestinal epithelial barrier, increased gut permeability, and an influx of immune cells. Given that most cellular functions as well as maintenance of the epithelial barrier is energy-dependent, it is logical to assume that mitochondrial dysfunction may play a key role in both the onset and recurrence of disease. Indeed several studies have demonstrated evidence of mitochondrial stress and alterations in mitochondrial function within the intestinal epithelium of patients with IBD and mice undergoing experimental colitis. Although the hallmarks of mitochondrial dysfunction, including oxidative stress and impaired ATP production are known to be evident in the intestines of patients with IBD, it is as yet unclear whether these processes occur as a cause of consequence of disease. We provide a current review of mitochondrial function in the setting of intestinal inflammation during IBD.

• autophagy
• gut-barrier function
• inflammasome
• inflammatory bowel disease
• intestinal inflammation
• metabolic stress
• mitochondrial dysfunction
• reactive oxygen species

The intestinal mucosa undergoes a continual process of proliferation, differentiation and apoptosis, which is regulated by multiple signaling pathways. Notch signaling is critical for the control of intestinal stem cell maintenance and differentiation. However, the precise mechanisms involved in the regulation of differentiation are not fully understood. Previously, we have shown that tuberous sclerosis 2 (TSC2) positively regulates the expression of the goblet cell differentiation marker, MUC2, in intestinal cells. Using transgenic mice constitutively expressing a dominant negative TSC2 allele, we observed that TSC2 inactivation increased mTORC1 and Notch activities, and altered differentiation throughout the intestinal epithelium, with a marked decrease in the goblet and Paneth cell lineages. Conversely, treatment of mice with either Notch inhibitor dibenzazepine (DBZ) or mTORC1 inhibitor rapamycin significantly attenuated the reduction of goblet and Paneth cells. Accordingly, knockdown of TSC2 activated, whereas knockdown of mTOR or treatment with rapamycin decreased, the activity of Notch signaling in the intestinal cell line LS174T. Importantly, our findings demonstrate that TSC2/mTORC1 signaling contributes to the maintenance of intestinal epithelium homeostasis by regulating Notch activity.

• Crohn’s disease
• Histopathology
• Molecular biology
• Pediatric inflammatory bowel disease
• Ulcerative disease

• Adolescent
• Age of Onset
• Algorithms
• Child
• Colitis, Ulcerative/classification
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/genetics
• Colitis, Ulcerative/pathology
• Colitis, Ulcerative/therapy
• Crohn Disease/classification
• Crohn Disease/diagnosis
• Crohn Disease/genetics
• Crohn Disease/pathology
• Crohn Disease/therapy
• DNA Mutational Analysis
• Diagnosis, Differential
• Genetic Markers
• Genetic Predisposition to Disease
• Genetic Testing/methods
• Humans
• Intestines/pathology
• Mutation
• Phenotype
• Predictive Value of Tests
• Prognosis

To reduce medication for patients with ulcerative colitis (UC), we need to establish the etiology of UC. The intestinal microbiota of patients with inflammatory bowel disease (IBD) has been shown to differ from that of healthy controls and abundant data indicate that it changes in both composition and localization. Small intestinal bacterial overgrowth is significantly higher in IBD patients compared with controls. Probiotics have been investigated for their capacity to reduce the severity of UC. The luminal surfaces of the gastrointestinal tract are covered by a mucus layer. This normally acts as a barrier that does not allow bacteria to reach the epithelial cells and thus limits the direct contact between the host and the bacteria. The mucus layer in the colon comprises an inner layer that is firmly adherent to the intestinal mucosa, and an outer layer that can be washed off with minimal rinsing. Some bacteria can dissolve the protective inner mucus layer. Defects in renewal and formation of the inner mucus layer allow bacteria to reach the epithelium and have implications for the causes of colitis. In this review, important elements of UC pathology are thought to be the intestinal bacteria, gut mucus, and the mucosa-associated immune system.

• Ulcerative colitis
• Mucus
• Infection
• Bacteria
• Etiology

• Animals
• Anti-Bacterial Agents/therapeutic use
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/microbiology
• Colitis, Ulcerative/therapy
• Colon/drug effects
• Colon/microbiology
• Colon/pathology
• Humans
• Intestinal Mucosa/drug effects
• Intestinal Mucosa/microbiology
• Intestinal Mucosa/pathology
• Microbiota
• Mucus/microbiology
• Probiotics/therapeutic use
• Risk Factors
• Treatment Outcome

• Anti-inflammation
• Antioxidation
• Edible plant exosomes
• Intestinal macrophages
• Nrf2

• Animals
• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics
• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism
• Cell Communication
• Cell Line, Tumor
• Citrus paradisi/chemistry
• Daucus carota/chemistry
• Exosomes/metabolism
• Gastrointestinal Tract/cytology
• Gastrointestinal Tract/metabolism
• Zingiber officinale/chemistry
• Heme Oxygenase-1/genetics
• Heme Oxygenase-1/metabolism
• Homeostasis
• Interleukin-10/genetics
• Interleukin-10/metabolism
• Intestines/drug effects
• Intestines/enzymology
• Macrophages/metabolism
• Mice
• Mice, Inbred C57BL
• NF-E2-Related Factor 2/genetics
• NF-E2-Related Factor 2/metabolism
• Nanoparticles/chemistry
• Particle Size
• Plants, Edible/chemistry
• Transcription Factor 4
• Vitis/chemistry
• Wnt Signaling Pathway
• beta-Galactosidase/metabolism

• VA999999 Intramural VA
• R01 AT004294 NCCIH NIH HHS
• UH2 TR000875 NCATS NIH HHS
• UH3 TR000875 NCATS NIH HHS
• R01 AT008617 NCCIH NIH HHS
• I01 BX000962 BLRD VA
• UH2TR000875 NCATS NIH HHS
• R01AT004294 NCCIH NIH HHS

Stem cells (SCs) are the key to tissue genesis and regeneration. Given their central role in homeostasis, dysfunctions of the SC compartment play a pivotal role in the development of cancers, degenerative disorders, chronic inflammatory pathologies and organ failure. The gastrointestinal tract is constantly exposed to harsh mechanical and chemical conditions and most of the epithelial cells are replaced every 3 to 5 d. According to the so-called Unitarian hypothesis, this renewal is driven by a common intestinal stem cell (ISC) residing within the crypt base at the origin of the crypt-to-villus hierarchical migratory pattern. Celiac disease (CD) can be defined as a chronic immune-mediated disease that is triggered and maintained by dietary proteins (gluten) in genetically predisposed individuals. Many advances have been achieved over the last years in understanding of the pathogenic interactions among genetic, immunological and environmental factors in CD, with a particular emphasis on intestinal barrier and gut microbiota. Conversely, little is known about ISC modulation and deregulation in active celiac disease and upon a gluten-free diet. Nonetheless, bone marrow-derived SC transplantation has become an option for celiac patients with complicated or refractory disease. This manuscript summarizes the “state of the art” regarding CD and ISCs, their niche and potential role in the development and treatment of the disease.

• Intestinal stem cells
• CD133
• Lgr5
• Celiac disease
• Paneth cells
• Gut microbiota
• Gut barrier

• Animals
• Basic Helix-Loop-Helix Transcription Factors/genetics
• Basic Helix-Loop-Helix Transcription Factors/metabolism
• Bifidobacterium
• Cell Differentiation/physiology
• Cell Line, Tumor
• Colon/cytology
• Colon/metabolism
• Colon/microbiology
• Escherichia coli
• Goblet Cells/cytology
• Goblet Cells/metabolism
• Goblet Cells/microbiology
• Homeodomain Proteins/genetics
• Homeodomain Proteins/metabolism
• Humans
• Kruppel-Like Factor 4
• Kruppel-Like Transcription Factors/genetics
• Kruppel-Like Transcription Factors/metabolism
• Lactobacillus
• Mice
• Mice, Inbred C57BL
• Mucin-1/genetics
• Mucin-1/metabolism
• Mucin-2/genetics
• Mucin-2/metabolism
• Transcription Factor HES-1
• beta-Defensins/genetics
• beta-Defensins/metabolism

• intestinal mucus layer
• gut-mediated sepsis

Fibrosis is a chronic and progressive process characterized by an excessive accumulation of extracellular matrix (ECM) leading to stiffening and/or scarring of the involved tissue. Intestinal fibrosis may develop in several different enteropathies, including inflammatory bowel disease. It develops through complex cell, extracellular matrix, cytokine and growth factor interactions. Distinct cell types are involved in intestinal fibrosis, such as resident mesenchymal cells (fibroblasts, myofibroblasts and smooth muscle cells) but also ECM-producing cells derived from epithelial and endothelial cells (through a process termed epithelial- and endothelial-mesenchymal transition), stellate cells, pericytes, local or bone marrow-derived stem cells. The most important soluble factors that regulate the activation of these cells include cytokines, chemokines, growth factors, components of the renin-angiotensin system, angiogenic factors, peroxisome proliferator-activated receptors, mammalian target of rapamycin, and products of oxidative stress. It soon becomes clear that although inflammation is responsible for triggering the onset of the fibrotic process, it only plays a minor role in the progression of this condition, as fibrosis may advance in a self-perpetuating fashion. Definition of the cellular and molecular mechanisms involved in intestinal fibrosis may provide the key to developing new therapeutic approaches.

• Inflammatory bowel disease
• Intestinal fibrosis
• Extracellular matrix
• Molecular mediators
• Myofibroblasts
• Inflammatory cells
• Epithelial cells
• Mesenchymal cells
• Endothelial cells

• Children
• Colonic biopsy
• Inflammatory bowel disease
• Intestinal alkaline phosphatase
• Toll-like receptor

• Adolescent
• Age Factors
• Alkaline Phosphatase/analysis
• Alkaline Phosphatase/genetics
• Biopsy
• Blotting, Western
• Case-Control Studies
• Child
• Child, Preschool
• Colitis/enzymology
• Colitis/genetics
• Colon/enzymology
• Crohn Disease/enzymology
• Crohn Disease/genetics
• Down-Regulation
• Female
• Fluorescent Antibody Technique
• GPI-Linked Proteins/analysis
• GPI-Linked Proteins/genetics
• Humans
• Hungary
• Infant
• Intestinal Mucosa/enzymology
• Male
• RNA, Messenger/analysis
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Toll-Like Receptor 4/analysis

Inflammatory bowel diseases (IBD) are chronic disorders of the intestine with increasing incidence in Europe, Northern America and asiatic countries such as china. Thus, we have putted together these topic highlight articles to give insights into the current understanding of IBD pathogenesis, diagnostics and treatment.

• Inflammatory bowel disease
• Endoscopy
• Endomicroscopy
• Confocal laser endomicroscopy
• Cytokines
• Immune system
• Colorectal cancer
• Postoperative recurrence