• Colonic immune
• Gut microbiota
• Inflammation
• Mucosal barrier
• Oxidative stress
• Ulcerative colitis

• Animals
• Drugs, Chinese Herbal/pharmacology
• Mice
• Gastrointestinal Microbiome/drug effects
• Disease Models, Animal
• Dextran Sulfate
• Male
• Colitis, Ulcerative/drug therapy
• Colitis, Ulcerative/chemically induced
• Oxidative Stress/drug effects
• Mice, Inbred C57BL
• Colitis/drug therapy
• Colitis/chemically induced
• Intestinal Mucosa/drug effects
• Female

• Cancer treatment
• Cross-kingdom regulation
• Inflammation
• Intestinal homeostasis
• Plant-derived exosome-like nanoparticles
• miRNA delivery systems

• Humans
• MicroRNAs/administration & dosage
• MicroRNAs/genetics
• Neoplasms/drug therapy
• Neoplasms/genetics
• Neoplasms/therapy
• Exosomes
• Nanoparticles/administration & dosage
• Animals
• Drug Delivery Systems

• 82074450 National Natural Science Foundation of China
• 21A0243 Key Scientific Research Project of Hunan Education Department
• 22YS002 Key Project of Academician Workstation Guidance Project
• 2021ZXYJH11 Key Projects of First-class Discipline of Integrated Traditional Chinese and Western Medicine
• kq2202271 National Natural Science Foundation of Changsha City

• causal inference
• de-confounding
• longitudinal microbiome analysis
• multi-omic integration
• unfolding

• Humans
• Algorithms
• Microbiota/genetics
• Longitudinal Studies
• Gastrointestinal Microbiome/genetics
• Metabolomics
• Computational Biology/methods
• Multiomics

• 1R15AI128714-01 HHS | NIH | OSC | Common Fund (NIH Common Fund)
• Dissertation Year Fellowship University Graduate School, Florida International University (UGS)

• Humans
• Colorectal Neoplasms/microbiology
• Colorectal Neoplasms/etiology
• Gastrointestinal Microbiome/physiology
• Life Style
• Diet/methods
• Dysbiosis
• Obesity/microbiology
• Risk Factors
• Dietary Fiber/administration & dosage

• Causal inference
• Longitudinal microbiome analysis
• Multi-omic integration
• Unfolding
• de-confounding

• R15 AI128714 NIAID NIH HHS

• colorectal cancer
• immunology
• inflammatory bowel diseases
• nanomedicine
• photodynamic therapy
• reactive oxygen species

• Humans
• Colorectal Neoplasms/etiology
• Inflammatory Bowel Diseases/drug therapy
• Colitis, Ulcerative
• Intestines
• Photochemotherapy

• Humans
• China
• Gastrointestinal Microbiome
• Cell Physiological Phenomena
• Cross Reactions
• Bibliometrics
• Neoplasms

• Aeromonas
• Cetobacterium
• CyHV-2
• gut microbiota-mediated metabolites
• tryptophan metabolism

• NF-κB
• Toll-like receptors
• colorectal cancer
• gut microbes
• pattern recognition receptor

• Social Development - Health Care Project of Yangzhou, jiangsu Province
• High-level talent “six one projects” top talent scientific research project of jiangsu Province

• Crohn’s disease
• anti-paratuberculosis-nocardia polypeptide antibodies
• biomarker
• diagnosis performance

• T cell differentiation
• T cell transfer
• Wumei decoction
• chronic colitis
• gut microbiota

• gut microbiota
• immune barrier
• intestinal barrier
• periodontal pathogens
• tight junction

• Animals
• Bacteria/immunology
• Bacteria/metabolism
• Bacteria/pathogenicity
• Gastrointestinal Diseases/immunology
• Gastrointestinal Diseases/metabolism
• Gastrointestinal Diseases/microbiology
• Gastrointestinal Microbiome
• Host-Pathogen Interactions
• Humans
• Intestinal Mucosa/immunology
• Intestinal Mucosa/metabolism
• Intestinal Mucosa/microbiology
• Mouth/immunology
• Mouth/metabolism
• Mouth/microbiology
• Periodontal Diseases/immunology
• Periodontal Diseases/metabolism
• Periodontal Diseases/microbiology
• Permeability

• cigarette smoking
• intestinal microbiota dysbiosis
• lung–gut axis
• skin-gut axis
• systemic disorders

• Adult
• Animals
• Blotting, Western
• Chemokine CCL2/genetics
• Chemokine CCL2/metabolism
• Enzyme-Linked Immunosorbent Assay
• Female
• Fluorescent Antibody Technique
• Humans
• Inflammatory Bowel Diseases/genetics
• Inflammatory Bowel Diseases/metabolism
• Interleukin-1beta/metabolism
• Interleukin-6/metabolism
• Interleukin-8/metabolism
• Leupeptins/genetics
• Leupeptins/metabolism
• Male
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Neutrophils/metabolism
• Real-Time Polymerase Chain Reaction
• Ribonucleases/metabolism
• Transcription Factors/metabolism
• Tumor Necrosis Factor-alpha/metabolism
• Young Adult

• Adenoma
• Colon Cancer
• Immune Regulation
• Tumor Suppressor

Cellular senescence is a stress response of human cells that removes potentially harmful cells by initiating cell cycle arrest. Inducing senescence of tumor cells may be an effective tumor-inhibiting strategy. In this study we found that PIK3R3 could inhibit the cell senescence of colorectal cancer cells and promote cell proliferation through the p53/p21 signal pathway. PIK3R3 could bind to p53 and inhibit the binding of p53 to the p21 gene promoter region, and thus affecting the transcriptional activity of p21 gene. Our study has provided new evidence of the role of PIK3R3 in p53 regulation and inhibition of PIK3R3 may be one of the potential targets of tumor therapy.

• Colorectal cancer
• cell death
• cell death mechanism
• membrane transport
• metabolism
• microbiota
• short chain fatty acids

• colonic bacteria
• colonic fermentation
• enteric bacterial microflora
• gastric surgery
• obesity surgery

• Mycobiota
• colorectal carcinogenesis
• detection methods
• host-microbe interaction
• immunity

• complementary and alternative medicine
• herbal medications
• inflammatory bowel disease

• carcinogenesis
• colorectal cancer
• inflammation
• microbiota

• Carcinogenesis/genetics
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/microbiology
• Colorectal Neoplasms/therapy
• Epigenesis, Genetic
• Fecal Microbiota Transplantation/methods
• Fecal Microbiota Transplantation/trends
• Feces/microbiology
• Gastrointestinal Microbiome/physiology
• Host-Pathogen Interactions
• Humans
• Intestines/microbiology
• Intestines/pathology
• Microbiota/physiology

• SCFAs
• colorectal cancers
• glycolysis
• gut microbiota
• therapy

• chemoprevention
• colorectal cancer
• dietary compounds

• Animals
• Anticarcinogenic Agents/therapeutic use
• Chemoprevention/methods
• Colonic Neoplasms/drug therapy
• Colonic Neoplasms/prevention & control
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/prevention & control
• Humans

• PN-III-P2-2.1-PTE-2016-0149/19PTE - TUMFLOW Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii

Neutrophils have been found to play an important role in the pathogenesis of inflammatory bowel disease (IBD), and anti-TNF-α mAb (i.e., infliximab) therapy is demonstrated to be effective in the induction of clinical remission and mucosal healing in these patients. However, how anti-TNF-α mAb regulates the functions of neutrophils is still unknown. Herein, we found that anti-TNF-α therapy significantly downregulated infiltration of neutrophils in inflamed mucosa of IBD patients. Importantly, anti-TNF-α mAb could inhibit neutrophils to produce proinflammatory mediators, such as ROS, calprotectin, IL-8, IL-6, and TNF-α. These data indicate that TNF-α plays a critical role in the induction of mucosal inflammatory response, and that blockade of TNF-α modulates intestinal homeostasis through balancing immune responses of neutrophils.

• food antigens
• food-specific IgGs
• inflammatory bowel disease
• total serum IgE
• total serum IgG

• Adult
• Colitis, Ulcerative/blood
• Colitis, Ulcerative/etiology
• Crohn Disease/blood
• Crohn Disease/etiology
• Enzyme-Linked Immunosorbent Assay
• Female
• Food Hypersensitivity/blood
• Food Hypersensitivity/complications
• Food Hypersensitivity/drug therapy
• Gastrointestinal Agents/therapeutic use
• Humans
• Immunoglobulin E/blood
• Immunoglobulin G/blood
• Infliximab/therapeutic use
• Male
• Middle Aged
• Young Adult

Inflammatory genes serve a crucial role in the pathogenesis of inflammation-associated tumors. However, as recent studies have mainly focused on the effects of single inflammatory genes on colorectal cancer (CRC), but not on the global interactions between genes, the underlying mechanisms between inflammatory genes and CRC remain unclear. In the current study, two inflammation-associated networks were constructed based on inflammatory genes, differentially expressed genes (DEGs) in CRC vs. normal samples, and protein-protein interactions (PPIs). These networks included an inflammation-related neighbor network (IRNN) and an inflammation-related DEG network (IRDN). Notably, the results indicated that the inflammatory genes served as important CRC-associated genes in the IRNN. Certain inflammatory genes were more likely to be network hubs and exhibited higher betweenness centralities, indicating that these inflammatory hub genes had central roles in the communication between genes in the IRNN. By contrast, in the IRDN, functional enrichment analysis revealed that genes were enriched in numerous cancer-associated functions and pathways. Subsequently, 14 genes in a module were identified in the IRDN as the potential biomarkers associated with disease-free survival (DFS) in CRC patients in the GSE24550 dataset, the prognosis of which was further validated using three independent datasets (GSE24549, GSE34551 and GSE103479). All 14 genes (including BCAR1, CRK, FYN, GRB2, LCP2, PIK3R1, PLCG1, PTK2, PTPN11, PTPN6, SHC1, SOS1, SRC and SYK) in this module were inflammatory genes, emphasizing the critical role of inflammation in CRC. In conclusion, these findings based on integrated inflammation-associated networks provided a novel insight that may help elucidate the inflammation-mediated mechanisms involved in CRC.

• Animals
• Biodiversity
• Fish Diseases/microbiology
• Fish Diseases/virology
• Gastrointestinal Microbiome
• Herpesviridae
• Herpesviridae Infections/veterinary
• Host-Pathogen Interactions
• Metagenome
• Metagenomics/methods
• RNA, Ribosomal, 16S
• ROC Curve

• IRT0848 the Program for Changjiang Scholars and Innovative Research Team in University, China

• CD177
• immunomodulation
• inflammatory bowel diseases
• neutrophils

Inflammatory bowel disease (IBD) including Crohn’s disease (CD) and ulcerative colitis is a relapsing-remitting illness. Patients with long-standing extensive colitis are easy to develop colorectal cancer (CRC). The increasing incidence of IBD and a substantial increase in the risk of CRC make the necessity to pay more attention on the regulation of inflammation especially by specific macrophages subset. The present study reported that a key subset of sinus macrophage expressing CD169 in mesenteric lymph nodes (mLNs) played an essential role in promoting mucosal inflammation. The results revealed that the subset expressing CD169 in mLNs increased significantly during the dextran sulfate sodium (DSS)-induced colitis. The colitic symptoms were alleviated in CD169-diphtheria toxin receptor (DTR) mice at least partially due to the deletion of CD169⁺ macrophages in mLNs. In addition, the levels of inflammatory cytokines as well as the percentage of Th17 cells in mLNs from CD169-DTR mice were much lower than those from WT mice with DSS-induced colitis. Further experiment in vitro demonstrated that the supernatant from whole cells of mLNs or colon tissues could promote the production of inflammatory factors by mLN cells or colon tissues from CD169-DTR mice. These results could be explained by the cell sorting result that CD11b⁺CD169⁺ macrophages expressed higher level of inflammatory factors directly. All these data indicated that CD169⁺ sinus macrophage in mLNs played an essential role on regulating mucosal inflammation.

• CD169+ macrophages
• colitis
• cytokines
• dextran sulfate sodium
• mesenteric lymph nodes

• gastrointestinal cancer
• liver
• nitric oxide

• HIF-1α
• IL-33
• inflammatory bowel disease

AIM: To determine serum levels of S100A12 in patients with ulcerative colitis (UC) and to explore its potential role in the diagnosis of UC and evaluation of disease development.

METHODS: Serum samples were collected from 66 patients with active UC (A-UC), 24 patients with UC in remission (R-UC) and 20 healthy controls. S100A12 levels were determined by ELISA. The role of S100A12 in the diagnosis and evaluation of disease development was then investigated.

RESULTS: The levels of serum S100A12 were significantly higher in patients with A-UC (725.6 pg/mL ± 239.6 pg/mL) compared with R-UC patients (311.2 pg/mL ± 87.5 pg/mL) and healthy controls (218.6 pg/mL ± 76.8 pg/mL) (P < 0.001). S100A12 was found to be markedly increased in severe UC patients compared with mild and moderate UC patients (P < 0.05). S100A12 was positively correlated with serum C-reactive protein (CRP) in UC patients. Moreover, S100A12 was found to be markedly decreased in UC patients after receiving effective treatment compared with that before treatment (P< 0.05).

CONCLUSION: S100A12 is markedly increased in the sera of UC patients. It can be used to diagnose the disease and predict the disease progression, suggesting that S100A12 is a useful marker for the prediction of UC.

• Ulcerative colitis
• Peripheral blood
• S100A12
• Diagnosis
• Prognosis

• Commensal A4 bacteria
• Dendritic cell
• TGF-β
• Th2

Divalent metal-ion transporter 1 (DMT1) has been found to play an important role in the iron metabolism and hemogenesis. However, little is known about the potential role of DMT1 in the pathogenesis of anemia from patients with inflammatory bowel disease (IBD). Herein, we investigated expression of DMT1 in the intestinal mucosa by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry, and found that DMT1 was significantly decreased in the inflamed mucosa of active IBD patients compared with that in those patients at remission stage and healthy controls. To further study the mechanism, we cultured HCT 116 cell line in vitro. Expression of DMT1 in HCT116 was demonstrated to be markedly decreased under stimulation with TNF for 24 and 48 h, while JNK inhibitor (JNK-IN-7) could significantly reverse the decrease. Interestingly, anti-TNF therapy successfully improved anemia in clinical responsive Crohn’s disease patients, and DMT1 was found to be markedly up-regulated in intestinal mucosa. Taken together, our studies demonstrate that decreased expression of DMT1 in intestinal mucosa leads to compromised absorption and transportation of iron and that blockade of TNF could rescue anemia and promote DMT1 expression in gut mucosa. This work provides a therapeutic approach in the management of anemia in IBD.

• CYTOKINES
• DENDRITIC CELLS
• IBD BASIC RESEARCH
• MUCOSAL IMMUNITY
• T LYMPHOCYTES

• Adaptive Immunity
• Animals
• B-Lymphocytes, Regulatory/immunology
• Bacteria/immunology
• Gastrointestinal Microbiome/immunology
• Humans
• Immunity, Innate
• Inflammatory Bowel Diseases/immunology
• Inflammatory Bowel Diseases/microbiology
• Inflammatory Bowel Diseases/pathology
• Intestines/immunology
• Intestines/microbiology
• Intestines/pathology
• T-Lymphocytes, Regulatory/immunology
• T-Lymphocytes, Regulatory/pathology

• R01 DK079918 NIDDK NIH HHS
• R01 DK098370 NIDDK NIH HHS
• DK079918 NIDDK NIH HHS
• DK098370 NIDDK NIH HHS

Objectives. Interactions between the host and gut microbial community contribute to the pathogenesis of Crohn's disease (CD). In this study, we aimed to detect lipopolysaccharide (LPS) and 1,3-β-D-glucan (BG) in the sera of CD patients and clarify the potential role in the diagnosis and therapeutic approaches. Materials and Methods. Serum samples were collected from 46 patients with active CD (A-CD), 22 CD patients at remission stage (R-CD), and 20 healthy controls, and the levels of LPS, BG, and TNF in sera were determined by ELISA. Moreover, sixteen patients with A-CD received anti-TNF monoclonal antibody therapy (infliximab, IFX) at a dose of 5 mg/kg body weight at weeks 0, 2, and 6, and the levels of LPS and BG were also tested at week 12 after the first intravenous infusion. Results. Serum levels of LPS and BG were found to be markedly increased in A-CD patients compared with R-CD patients and healthy controls (P < 0.05). They were also observed to be positively correlated with CDAI, ESR, and SES-CD, respectively (P < 0.05). Furthermore, the levels of TNF in sera had a significant correlation with LPS and BG, respectively. The concentrations of LPS and BG were demonstrated to be significantly downregulated in the sera of A-CD patients 12 weeks after IFX treatment (P < 0.05), suggesting that blockade of TNF could inhibit bacterial endotoxin absorption, partially through improving intestinal mucosal barrier. Conclusions. Serum levels of LPS and BG are significantly increased in A-CD patients and positively correlated with the severity of the disease. Blockade of intestinal mucosal inflammation with IFX could reduce the levels of LPS and BG in sera. Therefore, this study has shed some light on measurement of serum LPS and BG in the diagnosis and treatment of CD patients.

This study was undertaken to evaluate the efficacy of infliximab (IFX) in treatment of Crohn's disease (CD) patients. 106 CD patients were undergoing treatment with IFX from five hospitals in Shanghai, China. Clinical remission to IFX induction therapy was defined as Crohn's disease activity index (CDAI) < 150. Clinical response was assessed by a decrease in CDAI ≥ 70, and the failure as a CDAI was not significantly changed or increased. Ten weeks after therapy, 61 (57.5%) patients achieved clinical remission, 17 (16.0%) had clinical response, and the remaining 28 (26.4%) were failed. In remission group, significant changes were observed in CDAI, the Simple Endoscopic Score for Crohn's Disease (SES-CD), and serum indexes. Patients with short disease duration (22.2 ± 23.2 months) and luminal lesions showed better effects compared to those with long disease duration (71.0 ± 58.2 months) or stricturing and penetrating lesions. IFX markedly downregulated Th1/Th17-mediated immune response but promoted IL-25 production in intestinal mucosa from remission group. No serious adverse events occurred to terminate treatment. Taken together, our studies demonstrated that IFX is efficacious and safe in inducing clinical remission, promoting mucosal healing, and downregulating Th1/Th17-mediated immune response in short course CD patients with luminal lesions.

• Colitis
• Runx1
• TGF-β
• Th1
• Th17

The population tends to consume foods that in addition to their nutritional values can offer some benefits to their health. There are many epidemiological evidences and research studies in animal models suggesting that diet plays an important role in breast cancer prevention or progression. This review summarized some of the relevant researches about nutrition and cancer during the last years, especially in breast cancer. The analysis of probiotics and fermented products containing lactic acid bacteria in cancer prevention and/or treatment was especially discussed. It was observed that a balance of fatty acids similar to those of traditional Mediterranean diet, the consumption of fruits and vegetables, dietary fiber intake, vitamin supplementation are, along with the intake of probiotic products, the most extensively studied by the negative association to breast cancer risk. The consumption of probiotics and fermented products containing lactic acid bacteria was associated to reduce breast cancer risk in some epidemiological studies. The use of animal models showed the modulation of the host’s immune response as one of the important effects associated to the benefices observed with most probiotics. However; future assays in human are very important before the medical community can accept the addition of probiotic or fermented milks containing lactic acid bacteria as supplements for cancer patients.

• Breast cancer
• Nutrition
• Probiotic
• Fermented products

• Clostridium difficile
• Escherichia coli O157
• Staphylococcus aureus
• inflammatory bowel disease
• salmonella
• toxin