• B cells
• IL-10
• IL-10R
• central nervous system
• environmental factors
• experimental autoimmune encephalomyelitis
• multiple sclerosis

• Animals
• Interleukin-10
• Neuroinflammatory Diseases
• B-Lymphocytes
• Central Nervous System
• Multiple Sclerosis/etiology
• Receptors, Interleukin-10

• acute myeloid leukemia
• beta-catenin
• interacting protein

• Adaptor Proteins, Signal Transducing/genetics
• Humans
• Leukemia, Myeloid, Acute/drug therapy
• Leukemia, Myeloid, Acute/genetics
• Prognosis
• beta Catenin/metabolism

Caffeic acid (CA) is one of the major phenolic acids of coffee with multiple biological activities. Our previous study found that 500 mg/kg of chlorogenic acid (CGA) had the potential capacity of alleviating colonic inflammation. Moreover, CGA can be degraded into caffeic acid (CA) by the gut microbiota in the colon. Therefore, we hypothesize that CA can exert protective effects on colonic inflammation. To test the hypothesis, 251 mg/kg CA was supplemented to DSS-induced colitis mice. The results showed that CA treatment recovered DSS-induced disease activity index (DAI), colon length, and histopathology scores of colon tissue. Additionally, CA treatment significantly decreased pro-inflammatory cytokines and malondialdehyde (MDA) levels and increased the level of IL-10, total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in serum. qPCR results indicated that CA treatment dramatically downregulated mRNA expression of IL-1β, IL-6, and TNF-α as well as upregulated SOD1, GPX1, GPX2, CAT, and IL-10. In addition, CA supplementation significantly increased mRNA expression of Nrf-2, HO-1, and NQO1, which showed its antioxidant and anti-inflammatory capacities potentially by activating the Nrf-2/HO-1 pathway. Moreover, CA supplementation prevented gut barrier damage by enhancing Occludin gene expression. Furthermore, CA supplementation altered the gut microbiome composition by decreasing the relative abundance of Bacteroides and Turicibacter, and enhancing the relative abundance of Alistipes and Dubosiella. Meanwhile, CA supplementation increases the abundance of Dubosiella and Akkermansia. In conclusion, CA supplementation could effectively alleviate DSS-induced colitis by improving the defense against oxidative stress and inflammatory response.

• caffeic acid
• colitis
• gut microbiota
• inflammatory responses
• oxidative stress

• Allergy
• Autoimmune disease
• Blimp-1
• GWAS
• Human
• IL-10
• Infection
• Inflammatory bowel disease
• Intestinal homeostasis
• Regulatory T cell
• T cell
• Transcriptional regulation
• Tumor
• c-Maf

To investigate the correlation between the level of serum β-catenin and the disease progression of colorectal polyp (CRP) and colorectal cancer (CRC) and find its potential diagnostic value.

A total of 327 clinical serum samples and their electronic medical records were collected. Detecting by enzyme-linked immunosorbent assay (ELISA), the correlations of serum β-catenin with tumor marker carcinoembryonic antigen (CEA) and CRC clinicopathological parameters and the receiver operating characteristic (ROC) curve were analyzed.

Serum β-catenin levels in the CRP and CRC patients were significantly higher than those in the healthy control (HC) group (P < 0.05 and P < 0.001). Compared with CRP, serum β-catenin level in CRC was also increased (P < 0.05). However, there was no significant difference in gender, age, location, tumor size, Dukes staging, or metastasis (P > 0.05) between serum β-catenin and clinical parameters of CRC. There was no correlation between serum β-catenin levels and CEA in CRC patients (P = 0.14). ROC curve analysis showed that serum β-catenin possessed the maximum diagnostic efficiency in CRP (AUC = 0.73, P < 0.05) with 86.41% sensitivity and 51.56% specificity. β-Catenin combined with CEA had the highest diagnostic efficiency (AUC = 0.88, P < 0.05) with 81.88% sensitivity and 73.44% specificity. With CRC patients from CRP patients, ROC analysis of the combining detection (AUC = 0.70, P < 0.05) had the 70% sensitivity and 84.5% specificity.

The serum β-catenin levels are gradually increased in CRP and CRC, while there is no correlation between its levels and CRC disease process. Single serum β-catenin or combined CEA would be one of the potential candidate biomarkers for colorectal disease diagnosis.

• Children
• Genetic defect
• IL-10
• Immunodeficiency
• Inflammatory bowel disease
• Interleukin-10 receptor

• colitic cancer
• dysplasia
• p53
• ulcerative colitis

• Animals
• Colitis, Ulcerative/complications
• Colitis, Ulcerative/genetics
• Colitis, Ulcerative/pathology
• Colon/pathology
• Colonic Neoplasms/diagnosis
• Colonic Neoplasms/etiology
• Colonic Neoplasms/genetics
• Colonic Neoplasms/pathology
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Mutation
• Tumor Suppressor Protein p53/analysis
• Tumor Suppressor Protein p53/genetics

• Gene mutation
• Inflammatory bowel disease
• Interleukin-10
• Interleukin-10 receptor

• Il-10 receptor
• Tunisia
• genetic polymorphism
• multiple sclerosis

About 10% of total colorectal cancers are associated with known Mendelian inheritance, as Familial Adenomatous Polyposis (FAP) and Lynch syndrome (LS). In these cancer types the clinical manifestations of disease are due to mutations in high-risk alleles, with a penetrance at least of 70%. The LS is associated with germline mutations in the DNA mismatch repair (MMR) genes. However, the mutation detection analysis of these genes does not always provide informative results for genetic counseling of LS patients. Very often, the molecular analysis reveals the presence of variants of unknown significance (VUSs) whose interpretation is not easy and requires the combination of different analytical strategies to get a proper assessment of their pathogenicity. In some cases, these VUSs may make a more substantial overall contribution to cancer risk than the well-assessed severe Mendelian variants. Moreover, it could also be possible that the simultaneous presence of these genetic variants in several MMR genes that behave as low risk alleles might contribute in a cooperative manner to increase the risk of hereditary cancer. In this paper, through a review of the recent literature, we have speculated a novel inheritance model in the Lynch syndrome; this could pave the way toward new diagnostic perspectives.

• FUT2 gene
• Interleukin 10 receptor
• NOD2 gene
• Pediatric inflammatory bowel disease
• Very early-onset inflammatory bowel disease

• ADAM Proteins/genetics
• Age of Onset
• Asian People/genetics
• Child
• Child, Preschool
• China
• Colitis, Ulcerative/genetics
• Crohn Disease/genetics
• DNA Mutational Analysis
• Female
• Fucosyltransferases/genetics
• High-Throughput Nucleotide Sequencing
• Humans
• Infant
• Inflammatory Bowel Diseases/genetics
• Interleukin-10/genetics
• Interleukin-10 Receptor alpha Subunit/genetics
• Interleukin-10 Receptor beta Subunit/genetics
• Male
• Multiplex Polymerase Chain Reaction
• Mutation
• Nod2 Signaling Adaptor Protein/genetics
• Receptors, G-Protein-Coupled/genetics
• Receptors, Interleukin/genetics
• Tumor Necrosis Factor Ligand Superfamily Member 15/genetics
• Galactoside 2-alpha-L-fucosyltransferase

Epithelial-to-mesenchymal transition (EMT) confers stem cell-like phenotype and more motile properties to carcinoma cells. During EMT, the expression of E-cadherin decreases, resulting in loss of cell-cell adhesion and increased migration. Expression of Twist1 and other pleiotropic transcription factors, such as Snail, is known to activate EMT. We established primary colon cancer cell cultures from samples of operated patients and validated cultures by cytogenetic and molecular biology approaches. Western blot assay, quantitative real-time PCR and immunofluorescence were performed to investigate the expression of E-cadherin, vimentin, β-catenin, cytokeratin-20 and -18, Twist1, Snail, CD44, cyclooxygenase-2 (COX2), Sox2, Oct4 and Nanog. Moreover, cell differentiation was induced by incubation with LiCl-containing medium for 10 days. We observed that these primary colorectal cancer (CRC) cells lost expression of the E-cadherin epithelial marker, which was instead expressed in cancer and normal colon mucosa of the same patient, while overexpressed vimentin (mesenchymal marker), Twist1, Snail (EMT markers) and COX2. Cytokeratin-18 was expressed both in tissues and cell cultures. Expression of stem cell markers, such as CD44, Oct4 and Nanog, were also observed. Following differentiation with the glycogen synthase kinase 3β (GSK3β) inhibitor LiCl, the cells began to express E-cadherin and, at once, Twist1 and Snail expression was strongly downregulated, suggesting a MET-reverting process. In conclusion, we established primary colon mesenchymal cancer cell cultures expressing mesenchymal and epithelial biomarkers together with high level of EMT transcription factors. We propose that they could represent a good model for studying EMT and its reverting mechanism, the mesenchymal-to-epithelial transition (MET). Our observation indicates that LiCl, a GSK3β inhibitor, induces MET in vitro, suggesting that LiCl and GSK3β could represent, respectively, interesting drug, and target for CRC therapy.

High-mobility group A1 (HMGA1) proteins are architectural chromatinic proteins, abundantly expressed during embryogenesis and in most cancer tissues, but expressed at low levels or absent in normal adult tissues. Several studies have demonstrated that HMGA1 proteins play a causal role in neoplastic cell transformation. The aim of this study was to investigate the role of these proteins in the control of cancer stem cells (CSCs), which have emerged as a preferred target in cancer therapy, because of their role in cancer recurrence. We observed that HMGA1 is overexpressed in colon tumour stem cell (CTSC) lines compared to normal and colon cancer tissues. We demonstrated that HMGA1 silencing in CTSCs increases stem cell quiescence and reduces self-renewal and sphere-forming efficiency (SFE). The latter, together with the upregulation and asymmetric distribution of NUMB, is indicative of the recovery of an asymmetric division pattern, typical of normal stem cells. We further found that HMGA1 transcriptionally regulates p53, which is known to control the balance between symmetric and asymmetric divisions in CSCs. Therefore, our data indicate a critical role for HMGA1 in regulating both self-renewal and the symmetric/asymmetric division ratio in CSCs, suggesting that blocking HMGA1 function may be an effective anti-cancer therapy.

• Interleukin 10 deficiency;
• Paediatric
• Very early onset inflammatory bowel disease;

• Endocytosis/exocytosis
• Nanomedicine
• Polystyrene nanoparticles
• Primary cell culture

• Chemoprevention
• Colorectal cancer
• Dietary supplementation
• Epithelial dysplasia
• Estrogen receptors
• Inflammatory bowel disease
• Phytoestrogens
• Ulcerative colitis

• Animals
• Anti-Inflammatory Agents/therapeutic use
• Anticarcinogenic Agents/therapeutic use
• Cell Transformation, Neoplastic/metabolism
• Colitis, Ulcerative/complications
• Colitis, Ulcerative/drug therapy
• Colitis, Ulcerative/metabolism
• Colorectal Neoplasms/etiology
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/prevention & control
• Estrogen Receptor beta/agonists
• Estrogen Receptor beta/metabolism
• Humans
• Phytoestrogens/therapeutic use
• Protective Factors
• Receptors, Estrogen/drug effects
• Receptors, Estrogen/metabolism
• Risk Factors
• Signal Transduction/drug effects