• APC-associated polyposis
• Colorectal cancer
• Crohn’s disease
• FAP
• Lynch syndrome
• Ulcerative colitis

• Humans
• Registries
• Adult
• Male
• Female
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/pathology
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/complications
• Neoplastic Syndromes, Hereditary/complications
• Neoplastic Syndromes, Hereditary/pathology
• Disease Progression
• Colorectal Neoplasms, Hereditary Nonpolyposis/pathology
• Middle Aged

• Chang-Wei-Qing
• Colitis-associated colorectal cancer
• Metabolites
• Microbiota
• PD-1 inhibitor

• ptkwws202002 Shanghai Putuo District Health and Health System Science and Technology Innovation Project
• 2021tszk01 Shanghai Putuo District Health and Health System Clinical Specialty Construction Project
• ZY[2021-2023]-0302 Shanghai Municipal Health Commission's Shanghai Further Accelerating Traditional Chinese Medicine Development Three-Year Action Plan Project

• Colitis
• Th17
• Th9
• colitis-associated colorectal cancer
• dysplasia

• HelseNord
• The Second Affiliated Hospital of Zhengzhou University

• CRC
• IBD
• commensal microbiome
• intestinal mucosal immunity
• mucosal vaccine
• oral tolerance

• Humans
• Gastrointestinal Microbiome/immunology
• Immunity, Mucosal/immunology
• Intestinal Mucosa/immunology
• Intestinal Mucosa/microbiology
• Animals
• Symbiosis/immunology
• Homeostasis/immunology

• 82072648 National Natural Science Foundation of China
• 81772542 National Natural Science Foundation of China
• BK20211508 Natural Science Foundation of Jiangsu Province
• 021414380500 Fundamental Research Funds for the Central Universities
• JQX21009 Nanjing Medical Science and Technique Development Foundation

• chromosomal instability
• colorectal cancer
• genomics
• microsatellite instability
• molecular subtypes
• serrated pathway

• Humans
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/therapy
• Microsatellite Instability
• Genomics
• Gene Expression Profiling

• immune-mediated disorder
• non-conventional dysplasia
• small intestinal carcinoma

• Humans
• Crohn Disease/genetics
• DNA Methylation
• Adenocarcinoma/genetics
• Adenocarcinoma/pathology
• Duodenal Neoplasms/genetics
• DNA Modification Methylases/genetics
• Hyperplasia
• Isocitrate Dehydrogenase/genetics
• Mutation
• Brain Neoplasms/pathology
• Prognosis
• Tumor Suppressor Proteins/genetics
• DNA Repair Enzymes/genetics

• Italian Ministry of Health
• Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Policlinico San Matteo, Pavia, Italy
• Italian Ministry of Education, University and Research (MIUR)
• Department of Molecular Medicine of the University of Pavia
• Dipartimenti di Eccellenza (2018-2022)

• Humans
• Crohn Disease/metabolism
• Neuroglia/pathology
• Neurons/pathology
• Enteric Nervous System/metabolism
• Enteric Nervous System/pathology

• 2023-E-13 2022 Baoshan Medical and Health Project
• BSZK-2023-Z06 The Most Important Discipline, Baoshan Medical Key Discipline and Characteristic Brand Construction Project
• RJPY-LX-004 Cultivation Funding for Clinical Scientific Research Innovation, Renji Hospital, School of Medicine, Shanghai Jiaotong University

• colitis-associated colorectal cancer
• inflammatory bowel disease
• mechanism
• review
• traditional Chinese medicine formula

• 3D culture model
• cancer
• chronic inflammation
• decellularization
• extracellular matrix

• Adenocarcinoma/pathology
• Colorectal Neoplasms/pathology
• Follow-Up Studies
• Humans
• Hyperplasia
• Immunohistochemistry
• Inflammatory Bowel Diseases/pathology
• Matrix Attachment Region Binding Proteins
• Transcription Factors

Patients with ulcerative colitis are at an increased risk of developing colorectal cancer with a prolonged disease course. Many studies have shown that alterations in the immune microenvironment play a key role in ulcerative colitis-associated colorectal cancer. Additionally, competing endogenous RNAs have important functions in immunoregulation, affecting inflammation and tumorigenesis. However, the complexity and behavioral characteristics of the competing endogenous RNA immunoregulatory network in ulcerative colitis-associated colorectal cancer remain unclear. We constructed a competing endogenous RNA immunoregulatory network to discover and validate a novel competing endogenous RNA immunoregulatory axis to provide insight into ulcerative colitis-associated colorectal cancer progression.

The competing endogenous RNA immunoregulatory network was constructed using differential expression analysis, weighted gene co-expression network analysis, and immune-related genes. Cmap was used to identify small-molecule drugs with therapeutic potential in ulcerative colitis-associated colorectal cancer. The ulcerative colitis-associated colorectal cancer-related pathways were identified by gene set variation and enrichment analysis. CIBERSORT, single-sample Gene Set Enrichment Analysis, and xCell were used to evaluate the infiltration of immune cells and screen hub immunocytes. The competing endogenous RNA immunoregulatory axis was identified by correlation analysis.

We identified 130 hub immune genes and constructed a competing endogenous RNA immunoregulatory network consisting of 56 long non-coding RNAs, four microRNAs, and six targeted hub immune genes. Four small-molecule drugs exerted potential therapeutic effects by reversing the expression of hub immune genes. Pathway analysis showed that the NF-κB pathway was significantly enriched. Neutrophils were identified as hub immunocytes, and IL6ST was significantly positively correlated with the neutrophil count. In addition, NEAT1 may serve as a competing endogenous RNA to sponge miR-1-3p and promote IL6ST expression.

The competing endogenous RNA immunoregulatory axis may regulate neutrophil infiltration, affecting the occurrence of ulcerative colitis-associated colorectal cancer.

The online version contains supplementary material available at 10.1186/s12876-022-02252-7.

Huanglian jiedu decoction (HLJDD) is a heat-clearing and detoxifying agent composed of four kinds of Chinese herbal medicine. Previous studies have shown that HLJDD can improve the inflammatory response of ulcerative colitis (UC) and maintain intestinal barrier function. However, its molecular mechanism is not completely clear. In this study, we verified the bioactive components (BCI) and potential targets of HLJDD in the treatment of UC using network pharmacology and molecular docking, and constructed the pharmacological network and PPI network. Then the core genes were enriched by GO and KEGG. Finally, the bioactive components were docked with the key targets to verify the binding ability between them. A total of 54 active components related to UC were identified. Ten genes are very important to the PPI network. Functional analysis showed that these target genes were mainly involved in the regulation of cell response to different stimuli, IL-17 signal pathway and TNF signal pathway. The results of molecular docking showed that the active components of HLJDD had a good binding ability with the Hub gene. This study systematically elucidates the “multi-component, multi-target, multi-pathway” mechanism of anti-UC with HLJDD for the first time, suggesting that HLJDD or its active components may be candidate drugs for the treatment of ulcerative colitis.

Cancer cells, as well as surrounding stromal and inflammatory cells, form an inflammatory tumor microenvironment (TME) to promote all stages of carcinogenesis. As an emerging post-translational modification (PTM) of serine and threonine residues of proteins, O-linked-N-Acetylglucosaminylation (O-GlcNAcylation) regulates diverse cancer-relevant processes, such as signal transduction, transcription, cell division, metabolism and cytoskeletal regulation. Recent studies suggest that O-GlcNAcylation regulates the development, maturation and functions of immune cells. However, the role of protein O-GlcNAcylation in cancer-associated inflammation has been less explored. This review summarizes the current understanding of the influence of protein O-GlcNAcylation on cancer-associated inflammation and the mechanisms whereby O-GlcNAc-mediated inflammation regulates tumor progression. This will provide a theoretical basis for further development of anti-cancer therapies.

• Humans
• Inflammation
• N-Acetylglucosaminyltransferases/metabolism
• Neoplasms
• Protein Processing, Post-Translational
• Proteins/metabolism
• Signal Transduction
• Tumor Microenvironment

• Shenzhen Science and Technology Innovation Program
• National Natural Science Foundation of China

• Cancers
• Circulating adiponectin
• Mendelian randomization study
• Osteoporosis

• Adiponectin/genetics
• Bone Density/genetics
• Breast Neoplasms
• Genome-Wide Association Study
• Humans
• Male
• Mendelian Randomization Analysis
• Osteoporosis/genetics
• Polymorphism, Single Nucleotide/genetics

• Crohn’s disease
• WCGNA
• bioinformatics analysis
• ceRNA network
• experimental colitis mice model
• validation

• IBD-associated fibrosis
• colitis-associated colorectal cancer
• cross-talk
• glial cell-derived neurotrophic factor
• inflammatory bowel disease
• relapse

• Bias
• cohort study
• colorectal cancer
• inflammatory bowel disease
• proportional hazards models
• survival analysis

• Cohort Studies
• Colitis, Ulcerative
• Colorectal Neoplasms/epidemiology
• Crohn Disease
• Humans
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/drug therapy

• chronic ulcerative colitis
• inflammation
• inflammatory bowel disease

• Ulcerative colitis
• colorectal neoplasia
• histologic activity

• Cancer
• Colorectal cancer
• Crohn's disease
• Diagnosis
• Inflammatory bowel disease
• MicroRNA
• Prognosis
• Targets
• Ulcerative colitis

It is suggested that evolution has equipped humans and other species with powerful and, largely non-immunological resistance mechanisms that can nip pre-neoplastic cells, as well as cells disseminating from established tumors in the bud. These mechanisms must operate while maintaining tissue structure, polarity and a large variety of cell-to-cell interactions. Altogether, they are essential for microenvironmental tissue integrity. It has further been postulated that the genes underpinning microenvironmental control are not merely alleles of known cancer susceptibility genes, but constitute sui generis systems.

• colitis-associated colorectal cancer; CAC
• diagnostic model
• remission
• ulcerative colitis; UC

A specific diet regimen is a promising way of managing inflammatory bowel disease (IBD), with the Mediterranean diet (MD) being a likely candidate due to its potential to modulate gut inflammation. Therefore, the aim of this study was to investigate nutritional habits and dietary attitudes of IBD patients, and to assess their adherence to the Mediterranean diet. The study enrolled 50 Crohn’s disease and 44 ulcerative colitis patients, with clinical and laboratory parameters taken. Dietary attitudes were examined, and adherence to MD was assessed using the Mediterranean Diet Service Score (MDSS). Average MDSS score was 6.0 (5.0–7.0), while only nine participants fulfilled criteria for Mediterranean diet adherence. Moreover, all of them were men (p = 0.021). Low percentage of adherence to recommended guidelines was observed for eating olive oil (25.5%), fresh fruit (14.9%), and vegetables (10.6%). Significant positive correlation was observed between total MDSS points and high-density lipoprotein (HDL) cholesterol levels (p = 0.002). The majority of the patients (86.2%) considered that a more controlled diet could reduce their IBD symptoms, while 17% visited a nutritionist for diet advice. The majority of patients (84%) would visit educational programs regarding nutrition. In conclusion, adherence to MD was very low, while IBD patients were willing to extend their nutritional knowledge if proper educational programs were organized.

• Mediterranean Diet Service Score (MDSS)
• Mediterranean diet
• inflammatory bowel disease
• nutrition

• Adult
• Colitis, Ulcerative/diet therapy
• Crohn Disease/diet therapy
• Diet, Mediterranean
• Female
• Food
• Health Knowledge, Attitudes, Practice
• Humans
• Inflammatory Bowel Diseases/diet therapy
• Male
• Nutritional Status
• Patient Compliance

• colorectal cancer
• risk factors
• smoking
• ulcerative colitis

• Adult
• Aged
• Cohort Studies
• Colitis, Ulcerative/etiology
• Colitis, Ulcerative/physiopathology
• Colorectal Neoplasms/complications
• Colorectal Neoplasms/physiopathology
• Female
• Humans
• Male
• Middle Aged
• Proportional Hazards Models
• Retrospective Studies
• Risk Factors
• Survival Analysis

• Colitis-associated colorectal cancer
• NF-κB
• Single-Nucleotide Polymorphism (SNP)
• TNFα
• crohn's disease
• interleukin-1
• rs1800629
• ulcerative colitis

Nutraceuticals include a wide variety of bioactive compounds, such as polyphenols, which have been highlighted for their remarkable health benefits. Specially, maqui berries have shown great antioxidant activity and anti-inflammatory effects on some inflammatory diseases. The objectives of the present study were to explore the therapeutic effects of maqui berries on acute-phase inflammation in Crohn’s disease. Balb/c mice were exposed to 2,4,6-trinitrobenzene sulfonic acid (TNBS) via intracolonic administration. Polyphenolic maqui extract (Ach) was administered orally daily for 4 days after TNBS induction (Curative Group), and for 7 days prior to the TNBS induction until sacrifice (Preventive Group). Our results showed that both preventive and curative Ach administration inhibited body weight loss and colon shortening, and attenuated the macroscopic and microscopic damage signs, as well as significantly reducing transmural inflammation and boosting the recovery of the mucosal architecture and its muco-secretory function. Additionally, Ach promotes macrophage polarization to the M2 phenotype and was capable of down-regulating significantly the expression of inflammatory proteins COX-2 and iNOS, and at the same time it regulates the antioxidant Nrf-2/HO-1 pathway. In conclusion, this is the first study in which it is demonstrated that the properties of Ach as could be used as a preventive and curative treatment in Crohn’s disease.

• Crohn’s disease
• acute inflammation
• antioxidants
• inflammatory bowel disease
• inflammatory proteins
• macrophages
• maqui
• polyphenols

• Acute-Phase Reaction
• Administration, Oral
• Animals
• Anti-Inflammatory Agents
• Antioxidants
• Crohn Disease/chemically induced
• Crohn Disease/genetics
• Crohn Disease/prevention & control
• Crohn Disease/therapy
• Cyclooxygenase 2/metabolism
• Dietary Supplements
• Disease Models, Animal
• Fruit/chemistry
• Heme Oxygenase-1/metabolism
• Inflammation Mediators/metabolism
• Male
• Membrane Proteins/metabolism
• Mice, Inbred BALB C
• NF-E2-Related Factor 2/metabolism
• Nitric Oxide Synthase Type II/metabolism
• Nutritional Physiological Phenomena/physiology
• Phytotherapy
• Polyphenols/administration & dosage
• Polyphenols/isolation & purification
• Polyphenols/pharmacology
• Polyphenols/therapeutic use
• Signal Transduction/drug effects
• Signal Transduction/genetics
• Trinitrobenzenesulfonic Acid/adverse effects

Patients with chronic inflammatory bowel diseases are at an increased risk of developing colitis-associated cancer (CAC). Chronic inflammation positively correlates with tumorigenesis. Similarly, the cumulative rate of incidence of developing CAC increases with prolonged colon inflammation. Immune signaling pathways, such as nuclear factor (NF)-κB, prostaglandin E2 (PGE2)/cyclooxygenase-2 (COX-2), interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3), and IL-23/T helper 17 cell (Th17), have been shown to promote CAC tumorigenesis. In addition, gut microbiota contributes to the development and progression of CAC. This review summarizes the signaling pathways involved in the pathogenesis following colon inflammation to understand the underlying molecular mechanisms in CAC tumorigenesis.

• colitis-associated cancer
• colorectal cancer
• inflammatory bowel disease
• signaling pathway
• ulcerative colitis

Ulcerative colitis (UC) is characterized by relapsing–remitting inflammatory episodes paralleled by varying cytokine levels, suggesting that switching epigenetic processes might be involved. However, the epigenetic impact on cytokine levels in colitis is mostly unexplored. The heterodimeric interleukin (IL)-12 cytokine family have various functions in both pro- and anti-inflammatory processes. The family member IL-35 (EBI3/IL-12p35) was recently reported to play an anti-inflammatory role in UC. Therefore, we aimed to investigate a possible epigenetic regulation of the IL-35 subunits in vitro and in vivo, and to examine the epigenetic targeting of EBI3 expression as a therapeutic option for UC. Exposure to either the pro-inflammatory TNFα or to histone deacetylase inhibitors (HDACi) significantly increased EBI3 expression in Human Colon Epithelial Cells (HCEC) generated from healthy tissue. When applied in combination, a drastic upregulation of EBI3 expression occurred, suggesting a synergistic mechanism. Consequently, IL-35 was increased as well. In vivo, the intestines of HDACi-treated wild-type mice exhibited reduced pathological signs of colitis compared to non-treated colitic mice. However, the improvement by HDACi treatment was completely lost in Ebi3-deficient mice (Ebi3^−/−). In fact, HDACi appeared to exacerbate the disease phenotype in Ebi3^−/−. In conclusion, our results reveal that under inflammatory conditions, EBI3 is upregulated by the epigenetic mechanism of histone acetylation. The in vivo data show that the deficiency of EBI3 plays a key role in colitis manifestation. Concordantly, our data suggest that conditions promoting histone acetylation, such as upon HDACi application, improve colitis by a mechanism involving the local formation of the anti-inflammatory cytokine IL-35.

• Histone deacetylase inhibitor
• Inhibitory cytokines
• Interleukin-35
• SAHA
• Ulcerative colitis

• FTY720
• Fingolimod
• Inflammatory bowel disease
• Sphingosine kinase
• Sphingosine-1-phosphate
• Sphingosine-1-phosphate receptor
• Ulcerative colitis

• Animals
• Anti-Inflammatory Agents/pharmacology
• Fingolimod Hydrochloride/pharmacology
• Humans
• Inflammation/drug therapy
• Inflammation/metabolism
• Inflammatory Bowel Diseases/drug therapy
• Inflammatory Bowel Diseases/metabolism
• Protein Kinase Inhibitors/pharmacology
• Signal Transduction/drug effects
• Sphingolipids/antagonists & inhibitors
• Sphingolipids/metabolism

• Inflammatory bowel diseases
• cancer
• incidence

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/etiology
• Female
• Humans
• Incidence
• Inflammatory Bowel Diseases/complications
• Logistic Models
• Male
• Middle Aged
• Neoplasms/epidemiology
• Neoplasms/etiology
• Poisson Distribution
• Quebec/epidemiology
• Risk Factors
• Young Adult

• CAC
• CRC
• IBD
• miR-19a
• miR-21
• miR-31
• miRNAs

• angiogenesis
• apoptosis
• circadian rhythms
• colorectal cancer
• epigenetics
• inflammation
• melatonin

The present study planned to investigate the changes in the mRNA expression of inflammatory genes and their association with colorectal cancer (CRC). Our findings could be useful for noninvasive early screening of CRC patients.

Venous blood of 20 CRC cases and 15 healthy controls was collected. The mRNA expression of COX-2, TNF-α, NF-κB and IL-6 genes was carried out by using real-time polymerase chain reaction. Relative quantification was done to find out the fold change of these genes.

The mean age of cases and controls was 55 and 50 years, respectively. The ΔCt of COX-2, TNF-α, NF-κB and IL-6 genes was significantly (p < 0.05) lower in cases as compared to controls. Subsequently, the mRNA expression of these genes was, respectively, 3.56-, 3.4-, 1.71- and 3.86-fold higher in CRC cases as compared to controls. Positive correlation of ΔCt of COX-2 was found with ΔCt of TNF-α (r = 0.461, p = 0.041) and NF-κB (r = 0.536, p = 0.015) in CRC cases. The mRNA expression of COX-2 was significantly lower in T2 stage, while mRNA expression of NF-κB was significantly lower in both T2 and T3 stages of CRC as compared to T4 stage.

The increased mRNA expression of COX-2 along with the high mRNA expression of TNF-α, NF-κB and IL-6 genes may be associative risk factors for CRC. COX-2 and NF-κB genes were more expressed in advanced stages of CRC indicating their role in tumor progression. Our findings support the possible role of blood biomarker in the screening of CRC patients in the early stages.

• COX-2
• IL-6
• NF-κB
• TNF-α
• blood biomarker
• colorectal cancer
• mRNA expression

• Ulcerative colitis
• biomarker
• colitis-associated colorectal cancer
• endoscopy
• surveillance

• AOM/DSS mouse model
• NF-κB
• colitis-associated cancer
• wogonoside

• Anti-inflammatory
• Antiradical
• Maturity indices
• Polyphenols extracts
• Tunisian olive oil

• Animals
• Anti-Inflammatory Agents/chemistry
• Anti-Inflammatory Agents/pharmacology
• Antioxidants/chemistry
• Antioxidants/pharmacology
• Cell Survival
• Cells, Cultured
• Chromatography, High Pressure Liquid
• Free Radicals/chemistry
• Free Radicals/pharmacology
• Inhibitory Concentration 50
• Macrophages/drug effects
• Mass Spectrometry
• Mice
• Nitric Oxide/chemistry
• Nitric Oxide Synthase Type II/metabolism
• Olive Oil/chemistry
• Plant Oils/chemistry
• Plant Oils/pharmacology
• Polyphenols/chemistry
• Polyphenols/pharmacology

• Animals
• Colitis/metabolism
• Colorectal Neoplasms/metabolism
• Cyclooxygenase 2/metabolism
• Humans
• Inflammatory Bowel Diseases/metabolism
• Inflammatory Bowel Diseases/pathology
• Interleukin-23/metabolism
• Interleukin-6/metabolism
• NF-kappa B/metabolism
• STAT3 Transcription Factor/metabolism
• Signal Transduction/physiology

• Adenoma/pathology
• Adult
• Aged
• Biomarkers/metabolism
• Biopsy
• Colitis, Ulcerative/complications
• Colitis, Ulcerative/pathology
• Colon/pathology
• Colorectal Neoplasms/etiology
• Colorectal Neoplasms/pathology
• Diverticulitis, Colonic/complications
• Diverticulitis, Colonic/pathology
• Female
• High-Temperature Requirement A Serine Peptidase 1/metabolism
• Humans
• Immunohistochemistry
• Intestinal Mucosa/pathology
• Male
• Middle Aged
• Time Factors