Colorectal cancer (CRC) is a leading cause of cancer-related mortality, highlighting the need for early detection and accurate lesion characterization. Traditional white-light imaging has limitations in detecting lesions, particularly those with flat morphology or minimal color contrast with the surrounding mucosa. It also struggles to distinguish neoplastic from non-neoplastic lesions. These limitations led to the development of image-enhanced endoscopy (IEE). Image-enhanced endoscopy modalities such as narrow-band imaging, blue laser imaging, linked color imaging, and texture and color enhancement imaging enhance mucosal surface and vascular pattern visualization, thereby improving lesion detection and characterization. In contrast, red dichromatic imaging is primarily designed to enhance the visibility of deep blood vessels, making it particularly useful during therapeutic endoscopies, such as identifying bleeding sources and monitoring post-treatment hemostasis. Although IEE enhances lesion detection and characterization, it remains limited in assessing submucosal invasion depth, which is a key factor in treatment decisions. Endoscopic submucosal dissection requires accurate prediction of invasion depth; however, IEE mainly reflects superficial features. Endoscopic ultrasound and artificial intelligence-assisted diagnostics have emerged as complementary techniques for improving depth assessment and lesion classification. Additionally, IEE plays a critical role in detecting ulcerative colitis-associated neoplasia (UCAN), which often presents with a flat morphology and indistinct borders. High-definition chromoendoscopy and IEE modalities enhance detection; however, inflammation-related changes limit diagnostic accuracy. Artificial intelligence and molecular biomarkers may improve UCAN diagnosis. This review examines the role of IEE in lesion detection and treatment selection, its limitations, and complementary techniques such as endoscopic ultrasound and artificial intelligence. We also explored pit pattern diagnosis using crystal violet staining and discussed emerging strategies to refine colorectal cancer screening and management.

Fusobacterium nucleatum is a Gram-negative oncobacterium that is associated with colorectal cancer. The molecular mechanisms utilized by F. nucleatum to promote colorectal tumor development have largely focused on adhesin-mediated binding to the tumor tissue and on the pro-inflammatory capacity of F. nucleatum. However, the exact manner in which F. nucleatum promotes inflammation in the tumor microenvironment and subsequent tumor promotion remains underexplored. Here, we show that both living F. nucleatum and sterile F. nucleatum-conditioned medium promote CXCL8 release from the intestinal adenocarcinoma HT-29 cell line. We determined that the observed pro-inflammatory effect was ALPK1-dependent in both HEK293 and HT-29 cells and that the released F. nucleatum molecule had characteristics that match those of the pro-inflammatory ALPK1 ligand ADP-heptose or related heptose phosphates. In addition, we determined that not only F. nucleatum promoted an ALPK1-dependent pro-inflammatory environment but also other Fusobacterium species such as F. varium, F. necrophorum and F. gonidiaformans generated similar effects, indicating that ADP-heptose or related heptose phosphate secretion is a conserved feature of the Fusobacterium genus. By performing transcriptional analysis of ADP-heptose stimulated HT-29 cells, we found several inflammatory and cancer-related pathways to be differentially regulated, including DNA mismatch repair genes and the immune inhibitory receptor PD-L1. Finally, we show that stimulation of HT-29 cells with F. nucleatum resulted in an ALPK1-dependent upregulation of PD-L1. These results aid in our understanding of the mechanisms by which F. nucleatum can affect tumor development and therapy and pave the way for future therapeutic approaches.

The intestinal mucus barrier has emerged as a promising therapeutic target for inflammatory bowel disease. Understanding its regulatory mechanisms is critical for elucidating ulcerative colitis (UC) pathogenesis, improving diagnostics, guiding treatments, and preventing relapse. Chloride Channel Accessory 1 (Clca1), a constituent of the mucus layer, remains understudied in colitis. Here, we investigated Clca1's role in mucosal immunity and intestinal homeostasis using experimental colitis models. Clca1-deficient (Clca1-/-) mice displayed compromised mucus layer integrity, reduced neutrophil infiltration, and gut microbiota dysbiosis. Notably, Clca1-/- mice exhibited exacerbated colitis severity following dextran sulfate sodium (DSS) challenge, accompanied by a diminished goblet cell populations. Fecal microbiota transplantation (FMT) studies revealed that gut microbiota critically modulates divergent phenotypic outcomes between genotypes. Our findings establish Clca1 as a multifunctional regulator of mucus barrier integrity through mechanisms involving goblet cell maintenance, neutrophil-mediated immunity, and host-microbiota crosstalk. These results advance the understanding of UC pathogenesis and identify Clca1-associated pathways as potential targets for barrier restoration therapies.

Tumor necrosis factor-alpha (TNF-α) is an important target for the treatment of inflammatory diseases. Targeting TNF-α inhibition, such as antibody drug infliximab and adalimumab, has emerged as an effective therapeutic strategy for managing the most difficult-to-treat chronic ulcerative colitis (UC). So far, there are no small molecule TNF-α inhibitors available on the market for the treatment of UC. Previously, we reported an indanone analogue (R)-STU104 showed considerable inhibitory activity on TNF-α production in both acute and chronic mouse models of UC with a favorable safety profile. However, further development potential of this compound was greatly limited due to its poor metabolic stability in human liver microsomes and suboptimal pharmacokinetic profiles in mice. Herein, we discovered a deuterated TNF-α small molecule modulator (R)-104-6D-01, which demonstrated promising clinical potential for the treatment of UC. This new compound exhibited enhanced oral bioavailability and exposure in pharmacokinetic studies, as well as superior anti-UC efficacy in a DSS-induced mouse UC model, compared with (R)-STU104 at a dosage of 30 mg/kg/d. Collectively, (R)-104-6D-01 proves to be a promising candidate of potential use in treating UC as an oral TNF-α small molecule modulator.

The objective of this study is to explore the effect of adjuvant chemotherapy with toad venom injection in patients with intermediate and advanced colon cancer, in order to provide new reference drugs for clinical treatment. Prospectively, 148 patients with mid-stage to late-stage colon cancer in our hospital from January 2021 to May 2023 were selected for the study and randomly divided into two groups of 74 cases each. The control group was treated with FOLFOX4 chemotherapy, and the observation group was treated with four consecutive chemotherapy cycles based on the control group combined with toad venom injection. The treatment effects, adverse reactions, quality of life improvement rate, prognosis and cellular immune indexes [natural killer (NK) cells, CD4 + /CD8 + , CD4 + , CD3 + ], phosphatase tensin gene ( PTEN ), phosphatidylinositol-3-kinase (PI3k), and serine threonine protein kinase (pAKT) protein expression before and after treatment were counted in the two groups. The total effective rate of treatment in the observation group was 58.11% (43/74) after four cycles of chemotherapy, which was higher than that in the control group of 41.89% (31/74) ( P  < 0.05). After two cycles of chemotherapy and four cycles of chemotherapy, PTEN , CD4 + /CD8 + , CD4 + , CD3 + , and NK cells in peripheral blood were higher in the observation group than in the control group, and PI3k and pAKT were lower than in the control group ( P  < 0.05). There was no statistically significant difference in the rate of adverse reactions in the observation group compared with the control group ( P  > 0.05); the improvement rate of quality of life in the observation group was better than that in the control group after four chemotherapy cycles of treatment ( P  < 0.05); the survival rate was 75.00% (54/72) in the observation group compared with 54.29% (38/70) in the control group at 1-year follow-up. Toad venom injection adjuvant chemotherapy is effective in treating patients with intermediate and advanced colon cancer, which can upregulate PTEN level, inhibit PI3k and AKT expression, and improve immune function and quality of life of patients, thus improving prognosis.

Triclosan (TCS) and triclocarban (TCC) are widely used as antimicrobial agents in personal care products. Their widespread use has become a potential environmental contaminant. This review reviews the mechanisms of intestinal toxicity of TCS and TCC and their potential nutritional intervention strategies. TCS and TCC can be metabolized to glucuronic acid conjugates in the host and subsequently uncoupled by microorganisms in the intestine to regenerate free forms of TCS and TCC. TCS and TCC are unique metabolic pathways that lead to accumulation in the gut, altering the structure of intestinal flora, increasing the relative abundance of pathogenic bacteria, while reducing the abundance of beneficial bacteria, thereby disrupting the balance of intestinal flora. In addition, they can interfere with the self-renewal and differentiation of ISCs, thereby weakening intestinal barrier function. TCS and TCC can also activate the TLR4-NFκB signaling pathway, inducing and exacerbating inflammatory responses. These mechanisms together lead to intestinal toxicity and have a significant negative impact on intestinal health. In order to cope with the intestinal toxicity caused by these mechanisms of action, this paper believes that prebiotics, probiotics, vitamins, minerals and herbal extracts can be used as potential nutritional interventions to reduce the intestinal toxicity of TCS and TCC by regulating intestinal microbiota, enhancing intestinal barrier function and inhibiting inflammatory response. Although preliminary studies have shown the potential benefits of these interventions, their specific efficacy and safety still need further study.

This study evaluated the therapeutic effects of Xianliu Jieduan Fang (XLJDF) on colitis-associated colorectal cancer (CAC) and explored its molecular mechanisms through network pharmacology and experimental validation. Using an AOM/DSS-induced CAC mouse model, we evaluated XLJDF's efficacy. Active components were identified by UHPLC-QE-HRMS. Targets were predicted using SwissTargetPrediction and PubChem, while disease genes were obtained from GeneCards, DisGeNET, and TTD. Core targets and pathways were analyzed via Cytoscape and Metascape. Mechanisms were validated through molecular docking and experiments. XLJDF improved colon pathology and identified 68 active compounds, including nine key components like Kaempferol and Luteolin. Network analysis revealed 959 targets with 29 core genes (AKT1, CTNNB1, GSK3B, etc.). KEGG analysis showed XLJDF primarily acts through Wnt signaling, regulating apoptosis and cell migration. Experimental validation confirmed XLJDF inhibits Wnt/β-catenin pathway by preventing GSK3β inactivation. XLJDF exerts anti-CAC effects via a multi-component, multi-target network. Our study identifies key active compounds and demonstrates that XLJDF suppresses the Wnt/β-catenin pathway by preventing GSK3β inactivation, thereby inhibiting β-catenin stabilization.

Oxaliplatin resistance poses a significant challenge in colorectal cancer (CRC) treatment. Recent studies have implicated CPSF6 in cancer progression and drug resistance, although its role in chemotherapy resistance and regulatory mechanisms is unclear. This study investigates CPSF6's involvement in oxaliplatin resistance in CRC and its regulation via m6A methylation by METTL3. We assessed CPSF6 expression in oxaliplatin-resistant (OxR) CRC cell lines (HT29-OxR and HCT116-OxR) compared to sensitive counterparts using qRT-PCR and Western blotting. CPSF6 was significantly upregulated in OxR cells, and its knockdown reduced cell viability, colony formation, and glycolytic activity while increasing apoptosis. m6A modification of CPSF6 mRNA was elevated in OxR cells, correlating with increased METTL3 expression. METTL3 knockdown decreased CPSF6 levels and m6A enrichment, enhancing mRNA degradation, while its overexpression stabilized CPSF6 mRNA, promoting resistance. Xenograft experiments showed that CPSF6 knockdown suppressed tumor growth and glycolysis. Thus, CPSF6 is identified as a mediator of oxaliplatin resistance in CRC, regulated by the METTL3/m6A axis, suggesting potential therapeutic targets to overcome resistance.

Understanding the association between fibrinogen levels and cancer incidence is crucial for elucidating potential diagnostic and therapeutic implications in oncology.

This meta-analysis aimed to comprehensively evaluate the relationship between circulating fibrinogen levels and various tumour types.

This systematic review had been registered in PROSPERO (ID: CRD42024616015).

A systematic review search was performed on PUBMED, EMBASE and Cochrane databases until June 3, 2023.

Studies that fulfilled our pre-established inclusion criteria were incorporated into our analysis. These criteria encompassed prospective cohort, case-control, and nested case-control designs, all featuring histopathologically confirmed primary cancers. Furthermore, we included studies that had reported odds ratios (ORs), relative ratios (RRs) or hazard ratios (HRs) along with their corresponding 95% confidence intervals (95% CIs), ensuring the reliability and comparability of the data across studies.

Two independent authors meticulously extracted data from eligible studies, ensuring rigour and accuracy. Subsequently, we performed statistical analyses using the robust STATA version 12.0 software, guaranteeing the reliability of our findings. Moreover, we carried out in-depth subgroup analyses, categorizing studies based on tumour type, to meticulously explore and quantify the variations in the correlation between fibrinogen levels and tumour incidence. Through this approach, we have gained a nuanced understanding of the potential heterogeneity of this relationship across different cancer types.

The major outcome of this study centred on elucidating the relationship between fibrinogen levels and cancer incidence, with subsequent subgroup analyses conducted to delve deeper into this relationship within specific tumour types. This approach aimed to provide a comprehensive understanding of how fibrinogen levels may varying influence different cancer types, thereby offering potential insights into the identification of novel risk factors or biomarkers for further clinical investigation.

Twelve studies were meticulously incorporated into the meta-analysis. Notably, significant heterogeneity was observed across these studies, necessitating careful interpretation of the results. The meta-analysis demonstrated a compelling connection between elevated fibrinogen levels and an increased risk of cancer incidence, with an hazard ratio (HR) of 1.33 (95% CI: 1.16, 1.51; p = 0.000), demonstrating a statistically significant finding. Further subgroup analyses delved into specific cancer types and identified significant associations with smoking-related cancer (HR = 1.79; 95% CI: 1.54, 2.09; p = 0.000), lung cancer (HR = 1.98; 95% CI: 1.62, 2.43; p = 0.000) and colorectal cancer (HR = 1.27; 95% CI: 1.00, 1.62; p = 0.048). These findings underline the potential significance of fibrinogen levels as a potential biomarker or risk factor for these particular cancer types.

Elevated plasma fibrinogen levels have been significantly associated with an increased incidence of cancer, particularly in the cases of lung and colorectal cancers. These compelling findings underscore the potential value of fibrinogen levels as a diagnostic or prognostic biomarker in cancer management. Accordingly, further studies and clinical validation are urgently needed to fully explore the role of fibrinogen in cancer and its potential application in clinical practice.

Cancer metastasis is a primary contributor to cancer-related mortality, and mitigating the risk of metastasis has emerged as a central concern in oncology research. In recent years, exercise therapy, as a non-pharmacological intervention, has received considerable attention for its ability to enhance patients' quality of life and prognosis. Exercise significantly inhibits cancer spread, diminishes cancer risk, and improves therapy outcomes. Nonetheless, the exact mechanisms via which exercise inhibits the dissemination and metastasis of cancer cells are not fully elucidated. This review seeks to examine the mechanisms and prospective research avenues of exercise treatment in mitigating the risk of cancer metastasis. Moreover, it methodically examines pertinent clinical and scientific data, along with the efficacy of exercise therapies in real-world applications. The evaluation moreover suggests future research avenues, including a more profound exploration of mechanisms, the augmentation of clinical trials, the advancement of personalized and precision exercise therapy, and enhanced multidisciplinary collaboration. Exercise therapy shows significant potential in mitigating the risk of cancer metastasis, and its incorporation into holistic cancer treatment frameworks is advised to improve patients' general health and prognostic results.

The molecular mechanisms leading to inflammatory bowel disease (IBD) are only partially understood. We investigated the role of the transcription factor NFE2L3 in a mouse model of colitis by inducing inflammation using dextran sodium sulfate (DSS). We confirmed the presence of inflammation by histological analysis and elevated levels of the inflammation marker lipocalin-2 (LCN2) in the stool. We found that Lcn2 transcript levels are significantly less elevated in Nfe2l3-/- mice than wild type mice. We further showed a reduction of Nfe2l3 mRNA, in wildtype mice upon DSS treatment. We cross referenced ENCODE ChIP data of NFE2L3 binding partners MAFF and MAFK with known IBD and DSS effectors and identified Stat1, Hmox1, and Slc7a11 as potential NFE2L3 targets. These proteins are induced during colitis to suppress the immune response, reduce oxidative stress, and trigger ferroptosis, respectively. We analyzed the candidate targets and observed an increase in their protein expression upon DSS treatment in wild type but not in Nfe2l3-/- mice. Furthermore, in the absence of DSS, we observed an increase in the basal levels of pSTAT1 and SLC7A11 proteins in Nfe2l3-/- mice. These data suggest that the NFE2L3 transcription factor primes the microenvironment towards a pro-inflammatory ready state during inflammatory bowel disease (IBD).

In the progression from Inflammatory Bowel Disease to associated cancer, the clonal mutational landscape shifts from selection of mutations in inflammatory genes to selection of cancer-driver mutations1-4. How prevalence and expansion of either type of mutated clones could be impacted by the cellular environment in which they arise, and how this affects the neoplastic outcome of colitis is unknown. Here, we combine in vivo lineage tracing, in-silico modelling, mutational profiling and spatial transcriptomics in a mouse model of colitis-associated tumorigenesis to capture clone fates associated with chronic inflammation. We identify epithelial- and immune-enriched neighbourhoods and propose a model in which establishment of a reparative tissue environment facilitates tumours initiation by promoting the selection and expansion of pro-oncogenic clones, reducing the span of inflammation-resistant neighbourhoods containing non-oncogenic clones.

This study evaluates the efficacy of Lactobacillus plantarum (L. plantarum) NBRC15891 encapsulated in a W1/O/W2 emulsion stabilized by ultrasonically treated pea protein nanoparticles (HIU-PPI-NP) for alleviating colitis. The results indicate that HIU-PPI-NP effectively preserved bacterial viability during simulated gastrointestinal digestion, with a survival rate of 72.62 %, significantly higher than that of free bacteria (0.0017 %). In vivo, the L. plantarum-loaded emulsion alleviated dextran sodium sulfate (DSS) -induced colitis in mice by improving body weight, reducing the disease activity index (DAI), and decreasing myeloperoxidase (MPO) activity in the colonic tissue. Gene expression analysis revealed reduction in inflammation markers (TNF-α, IL-6) and restoration of MUC2 expression. Furthermore, microbiota analysis indicated that L. plantarum-loaded emulsion altered the microbiota composition by promoting beneficial genera, such as Lachnospiraceae_NK4A136_group and Eubacterium_siraeum_group, while inhibiting the pathogenic growth of Escherichia-Shigella. Additionally, an increase in short-chain fatty acid (SCFA) concentrations was observed in mice treated with the L. plantarum-loaded emulsion. Importantly, neither free L. plantarum cells nor L. plantarum-free emulsion exhibited comparable therapeutic effects on colitis, suggesting that this emulsion system could aid in protecting L. plantarum and enhancing its efficacy. These findings underscore the potential of HIU-PPI-NP-stabilized emulsion as a novel probiotic delivery system for gut health application.

Lysine demethylase 4D (KDM4D) and aberrant lipid metabolism are implicated in the development and progression of colitis-associated cancer (CAC). Moxibustion, a therapeutic approach in traditional Chinese medicine, can inhibit intestinal inflammation and improve the intestinal mucosa.

Mice were intraperitoneally injected with AOM, and three cycles of 3-2-2% DSS-free drinking water were administered to establish a CAC mouse model. Moxibustion and KDM4D inhibitor 5-c-8HQ intervention were performed for 30 days after modeling was completed. IHC staining was used to observe the expression of the nuclear-associated antigen Ki67 (Ki67), proliferating cell nuclear antigen (PCNA), and IL-33 in the colon. The expression of colon KDM4D and β-Catenin was observed by immunofluorescence staining and RT‒qPCR. LC‒MS pseudotargeted metabolomic sequencing was used to semiquantitatively detect the expression levels of lipids.

Moxibustion inhibited the proliferation of colon tumors in CAC mice, improved histopathology, and reduced the expression of PCNA and Ki67 in the colon. Using kdm4d knockout technology, it was initially confirmed that kdm4d is a key gene affecting CAC tumor proliferation. The inhibition of colon tumor proliferation in CAC mice by moxibustion is associated with the suppression of abnormal activation of the colon KDM4D/β-Catenin signaling pathway. LC-MS-targeted metabolomics revealed abnormal lipid metabolism in the colons of CAC mice. Moxibustion may affect the cholinergic metabolism pathway in the colon of CAC mice and regulate lipids such as sphingomyelin SM (d18:1/26:0) and triacylglycerol TAG58:7 (18:0). After kdm4d knockout, lipid disorders in the colons of CAC mice were partially restored. The kdm4d gene may be involved in the mechanism underlying the effect of moxibustion on lipid metabolism in the CAC colon.

Moxibustion inhibited the proliferation of colon tumors in CAC mice, inhibited the activation of the tumor-promoting signaling pathway KDM4D/β-Catenin, and improved lipid metabolism disorders in the colon, thus providing a promising strategy for the clinical adjuvant treatment of colorectal cancer.

Beetroot (Beta vulgaris L.) is well known for its medicinal uses, particularly in managing gastrointestinal disorders. This study investigates the protective effects of fresh red beet juice (FBRJ) on gastrointestinal complications caused by co-administration of dextran sulfate sodium (DSS) and loperamide (LOP), which induce ulcerative colitis and constipation, respectively.

Adult rats were divided into groups and subjected to a 7-day treatment with 5% DSS to induce ulcerative colitis, followed by LOP (3 mg/kg, body weight [b.w.]) for 7 days to cause constipation. FBRJ (5 and 10 mL/kg, b.w.) or yohimbine (YOH) (2 mg/kg, b.w.) was administered 1 h after LOP each day for 7 days. Therapeutic outcomes were evaluated based on macroscopic and histological changes in the gastrointestinal tract, gastric emptying, gastrointestinal transit, oxidative stress parameters, and inflammatory markers.

FBRJ significantly alleviated gastrointestinal dysfunctions caused by DSS and/or LOP, improving both gastric emptying and gastrointestinal transit in a dose-dependent manner (p < 0.05). Specifically, compared with the ulcerative/constipated group, the animals treated with the FBRJ showed a significant increase (52.43% ± 4.65% to 66.23% ± 6.78%) of gastric emptying (GE) andgastrointestinal transit (GIT: 48.08% ± 3.32% to 62.46% ± 4.98%) in a dose-dependent manner. It also modulated antioxidant defense systems by inducing enzyme activities and reducing lipid peroxidation, which had been significantly disrupted by the combined effects of DSS and LOP. Furthermore, inflammatory markers, including C-reactive protein (CRP), pro-inflammatory cytokines, and white blood cell counts, were significantly reduced in both plasma and colonic mucosa.

We suggest that FBRJ significantly protects against DSS-induced colitis and LOP-induced constipation, involving several mechanisms such as increasing secretion and peristaltic activity, reducing inflammation, and preserving the antioxidant properties.

Ulcerative colitis (UC) is an inflammatory colon and rectum disease affecting approximately 5 million people worldwide. There is no cure for UC, and approximately 8% of patients with UC develop colorectal cancer (CRC) by gradual acquisition of mutations driving the formation of adenomas and their progression to adenocarcinomas and metastatic disease. CRC constitutes 10% of total cancer cases worldwide and 9% of cancer deaths. Both UC and CRC have an increasing incidence worldwide. Although the epithelium has been well studied in UC and CRC, the contribution of neutrophils is less clear. Neutrophils are rapidly recruited in excessive amounts from peripheral blood to the colon during UC, and their overactivation in the proinflammatory UC tissue environment contributes to tissue damage. In CRC, the role of neutrophils is controversial, but emerging evidence suggests that their role depends on the evolution and context of the disease. The role of neutrophils in the transition from UC to CRC is even less clear. However, recent studies propose neutrophils as therapeutic targets for better clinical management of both diseases. This review summarizes the current knowledge on the roles of neutrophils in UC and CRC.

BRAF mutation affects the biological characteristics and microenvironment of the tumor during the development of colorectal cancer. Tumor-associated lymph nodes are the key sites of immune response. This study aimed to systematically evaluate the impact of BRAF gene mutations on the remodeling of the CRC immune microenvironment, with a particular focus on their effects on the maturation and function of TLS·In this study, clinical samples of CRC patients were collected, and immune cell subsets were analyzed by single-cell RNA sequencing, and pseudo-temporal locus analysis and spatial transcriptome analysis were performed to explore intercellular communication and functional enrichment analysis. The distribution and maturity of TLS were evaluated by immunohistochemistry and multiple fluorescence staining techniques, and statistical analysis was performed.The results showed that BRAF mutation significantly affected the number and maturity of lymphatic structures infiltrated by tumors, and was negatively correlated with patient prognosis. BRAF mutations lead to alterations in T cell subsets, particularly the dual role of CD4+ CXCL13 cells in TLS maturation. B-cell subpopulation analysis revealed functional deficits in CRC patients with BRAF mutations, which further drove the remodeling of the tumor immune microenvironment.

There is an urgent need to identify biomarkers of tumorigenesis for colitis-associated cancer (CAC) as early cancer detection remains crucial for patients with inflammatory bowel disease (IBD). This in silico study examines the relationship between IBD and CAC, with particular regard to differentially-expressed genes (DEGs).

Integrated bioinformatics tools and public databases were employed. Data from GEO (GSE102133, GSE48958, GSE9348, GSE83687, GSE138202) were processed using GEOexplorer. DEGs were then functionally annotated with DAVID, SRplot, and integrated analysis via Metascape. Validation used Oncopression and Human Protein Atlas. Survival analysis employed GEPIA2. miRNA interactions were studied via miRTargetLink 2.0. Immune infiltration was analyzed with TIMER 2.0. COL1A1 expression and mutations were examined using cBioPortal, Kaplan-Meier plotter, and DNA methylation was analyzed using MethSurv. Correlation of COL1A1 gene promoter methylation with tissue type and clinical data was performed using the UALCAN database. The ROC analysis of COL1A1 was conducted in the R environment.

Our analysis identified three potential hub genes (ICAM1, LAMC1, and COL1A1), which are overexpressed in IBD and cancer tissues compared to normal tissue, and hence may play a role in CAC. Furthermore, patients with lower COL1A1 expression had longer disease-free survival (p = 0.01) than those with higher expression. Therefore, this gene was chosen for further analysis and identified as the most crucial.

COL1A1 reveals significant immunohistochemistry, mutations, and methylation data. Further studies involving machine learning and clinical data are required to validate the results.

We herein present the case of a 30-year-old Japanese male patient with ulcerative colitis (UC) who was admitted to our hospital because of significant ascites. Upon evaluation, the patient was diagnosed with unresectable UC-associated colon cancer (UCAC), localized in the transverse colon. Using gene profiling of the tumor tissue, anti-epidermal growth factor receptor (EGFR) antibody combination chemotherapy was selected. Subsequently, the patient exhibited a temporary response to this regimen, with an enhancement in his quality of life and he was able to survive for 12 months. This case underscores the potential benefits of aggressive chemotherapy tailored to the gene profile in UCAC treatment, offering insights into potential avenues for improving the patient prognosis.

Patients with inflammatory bowel disease (IBD) remain at increased risk for colorectal cancer and death from colorectal cancer compared with the general population despite improvements in inflammation control with advanced therapies, colonoscopic surveillance and reductions in environmental risk factors. This guideline update from 2010 for colorectal surveillance of patients over 16 years with colonic inflammatory bowel disease was developed by stakeholders representing UK physicians, endoscopists, surgeons, specialist nurses and patients with GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodological support.An a priori protocol was published describing the approach to three levels of statement: GRADE recommendations, good practice statements or expert opinion statements. A systematic review of 7599 publications, with appraisal and GRADE analysis of trials and network meta-analysis, where appropriate, was performed. Risk thresholding guided GRADE judgements.We made 73 statements for the delivery of an IBD colorectal surveillance service, including outcome standards for service and endoscopist audit, and the importance of shared decision-making with patients.Core areas include: risk of colorectal cancer, IBD-related post-colonoscopy colorectal cancer; service organisation and supporting patient concordance; starting and stopping surveillance, who should or should not receive surveillance; risk stratification, including web-based multivariate risk calculation of surveillance intervals; colonoscopic modalities, bowel preparation, biomarkers and artificial intelligence aided detection; chemoprevention; the role of non-conventional dysplasia, serrated lesions and non-targeted biopsies; management of dysplasia, both endoscopic and surgical, and the structure and role of the multidisciplinary team in IBD dysplasia management; training in IBD colonoscopic surveillance, sustainability (green endoscopy), cost-effectiveness and patient experience. Sixteen research priorities are suggested.

Colitis-associated colon cancer (CAC) is a specific subset of colorectal cancer (CRC) affecting patients with inflammatory bowel diseases (IBDs). Chronic colon inflammation orchestrates immune surveillance or escape and may drive neoplastic initiation and progression. Lacticaseibacillus casei 393 (L. casei 393) is a lactic acid microorganism that, beyond its nutritional value, provides health benefits. To explore the therapeutic potential of this probiotic against CAC, we evaluated colon histopathology, circulating cytokines, and the expression of the Kristen rat viral sarcoma oncogene homolog (KRAS) and the adenomatosis polyposis coli (APC) tumor-suppressing gene in the murine model of CAC induced with azoxymethane (AOM) and dextran sodium sulfate (DSS).

BALB/c mice (n=7/group) received two doses of AOM (10 mg/kg body weight) followed by three 5-day cycles of 2% DSS. L. casei 393 was administered orally [1×106 colony forming units (CFU)/100 µL/mouse/twice a week/6 months] either alone, before AOM-DSS, or starting at the same time as AOM-DSS. Colon histopathology was assessed by hematoxylin-eosin staining, circulating cytokines by flow cytometry, and the expression of colonic KRAS and APC by quantitative reverse transcription polymerase chain reaction (RT-qPCR).

AOM-DSS induced CAC in BALB/c mice, which presented severe colon damage, high cytokine levels, and altered KRAS and APC expression. Conversely, L. casei 393 ingestions, starting at the same time as CAC induction, restored colon architecture and modulated cytokine levels and gene expression.

The present experimental work supports the therapeutic potential of L. casei 393 against CAC, as it shows that its ingestion restored the damaging effect of AOM-DSS through its anti-inflammatory properties that helped modulate KRAS and APC mRNA expression.

Colorectal cancer (CRC) is the third most common cancer in the world and the second cause of death related to cancer. Regulatory T cell (Treg) infiltration is enriched in several tumor types including CRC and correlates with suppression of the anti-tumor immune response. In the large intestine, thymic Tregs (tTregs Helios+) and peripheral Tregs (pTregs Helios-) coexist and maintain intestinal homeostasis under steady state conditions. The recruitment of Treg cells to the intestine is orchestrated by the CCR9/CCL25 axis, which is potentiated under inflammatory conditions. Interestingly, the balance between cytotoxic CD8+ T cells and Tregs within the tumor microenvironment is critical for antitumor immunity and cancer progression. An elevated CD8+/Treg ratio has been associated with improved clinical outcomes in various cancers, including CRC. Therefore, here we investigate the potential role of chemokine receptor CCR9 on CD8+/Treg ratio and the effect of the recruitment of Treg subpopulations (Helios+ and Helios-) into the tumor microenvironment using the AOM/DSS induced colitis-associated colorectal cancer murine model. Our findings reveal that CCR9 deficiency leads to distinct alterations in the CRC microenvironment, characterized by decreased intratumoral Tregs Helios+. Also, the lack of the receptor leads to an improvement of the antitumor immune response, increasing the CD8+/Treg ratio within the tumor immune infiltrate. These results underscore the importance of CCR9 in shaping the immune microenvironment during CRC development.

Characterized by elevated reactive oxygen species (ROS) and disrupted gut flora, ulcerative colitis (UC) affects millions of patients worldwide. Probiotic therapy is commonly utilized in clinical practice to modulate intestinal flora and ameliorate colitis symptoms. Nonetheless, oral probiotics encounter challenges such as limited bioactivity, brief retention time, intricate pathological conditions, and singular efficacy. Here we designed plant-derived 18β-glycyrrhetinic acid (18β-GA) prodrug nanomicelles with ROS and inflammation-resolving capabilities, as well as anti-depressant effects, to protect probiotics and amplify their therapeutic effects in alleviating UC and UC-associated depression-like behaviors. Upon oral administration to UC lesion sites, prodrug nanomicelles can be dissociated by excessive ROS and release 18β-GA to attenuate colonic inflammatory responses and oxidative stress, which in turn provided a favorable microenvironment for LGG to repair intestinal barrier integrity and restore the gut microbiota. The synergistic therapeutic effects of STG nanomicelles and LGG alleviated UC-associated depression-like behavior by suppressing the activation of microglia and reducing neuroinflammation. This study introduces a promising strategy for oral nanomedicine with satisfactory therapeutic outcomes for the treatment of inflammatory diseases by integrating naturally derived small-molecule drugs with probiotics.

Inflammatory bowel disease leads to increased risk of developing colitis-associated colon cancer (CAC). CMTM3 has a higher methylation level in colon cancer, and accumulating evidence suggests that chemokine-like factor-like MARVEL transmembrane domain-containing member 3 (CMTM3) participates in inflammation and cancer development.

We explored the signs of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC in wild-type (WT) and Cmtm3 deficiency (Cmtm3-/-) mice. Experimental colitis was induced in Cmtm3-/- mice as well as mice with endothelial cell-specific deletion of Cmtm3. Disease phenotypes were investigated by body weight, disease activity index (DAI), colon length, histology, immune cell infiltration, and intestinal permeability. The mechanism was analyzed using bone marrow reconstitution, immunofluorescent staining, Western blot, immunoprecipitation, and pull-down experiments.

We found CMTM3 promoted CAC by aggravating colitis. Further, we revealed endothelial cell-specific deletion of Cmtm3 inhibited the colitis development. In vitro and in vivo mechanistic studies revealed that CMTM3 drove colitis by increasing clathrin-dependent downregulation of vascular endothelial-cadherin, thus causing vascular permeability. We further identified that CMTM3 interacted with clathrin heavy chain and inhibited clathrin heavy chain ubiquitination and proteasome-dependent degradation. Interestingly, Cmtm3 knockout and imatinib mesylate both targeted vascular permeability and had comparable efficacy.

Our study indicates that CMTM3 promotes CAC by aggravating colitis through causing vascular permeability, providing insights into targets for development of future therapies.

The prevalence of night-shift employment is on the rise among full-time and part-time workers globally. Those engaged in night-shift work encounter various biological challenges, including exposure to artificial light during nighttime and disruptions to their circadian rhythms. These factors, along with changes in daily routines and activities, may pose significant risks to the health of night workers. Notably, the number of individuals working overtime or on night shifts has increased across various sectors, particularly in transportation, healthcare, and manufacturing. The International Agency for Research on Cancer (IARC) has classified night-shift work as probably carcinogenic to humans (IARC Group 2A). Subsequent research has identified several potential mechanisms through which night-shift work may contribute to carcinogenicity: (1) disruption of circadian rhythms, (2) suppression of melatonin levels due to nighttime light exposure, (3) physiological alterations, (4) lifestyle changes, and (5) reduced vitamin D levels resulting from inadequate sunlight exposure. Colorectal cancer (CRC) poses a significant public health challenge, ranking as the second leading cause of cancer-related death worldwide in 2020. Other than CRC, other gastrointestinal cancers are also creating a great global health issue because of their morbidity and mortality rates. In this review, we highlight the role of night shifts in disturbing circadian rhythm and how this action leads to carcinogenesis in the GI tract.

Inflammatory bowel disease (IBD) is an autoimmune disease of unknown etiology characterized by recurrent chronic inflammation of the gastrointestinal tract. The incidence of IBD is increasing and has become a focus of research on digestive diseases. Despite advances in understanding its multifactorial etiology, including genetic predisposition, microbiome dysbiosis, and immune dysregulation. However, the molecular mechanisms driving IBD pathogenesis remain incompletely elucidated. Circular RNA (circRNA) is a stable single-stranded RNA with a closed-loop structure and conserved nature. circRNA possesses multiple functions, such as adsorption of microRNAs and RNA-binding proteins, and is involved in the regulation of gene splicing and transcription, as well as protein translation. However, circRNAs in IBD progression and their clinical potential as biomarkers or therapeutic targets are yet to be systematically explored. In this review, we comprehensively synthesize recent advancements in circRNA research related to IBD, integrating evidence from in vitro, in vivo, and clinical studies. We systematically analyze aberrant circRNA expression profiles in IBD tissues (e.g., intestinal mucosa, peripheral blood, and exosomes) and discuss their mechanism of action contributions to inflammation, intestinal epithelial barrier dysfunction, autophagy, intestinal fibrosis, and colitis-associated cancer (CAC). Furthermore, we evaluate methodologies for circRNA detection and therapeutic modulation, including RNA interference, viral vector delivery, and PLGA MSs delivery system strategies. This review highlights the potential of circRNA-focused strategies in the diagnosis and treatment of IBD, offering a scientific foundation for advancing precision medicine in IBD management.

Gut microbiota can significantly alter the risk or progression of cancer by maintaining gut immune system homeostasis. However, the exact mechanism by which the gut microbiota and its metabolites influence colorectal tumorigenesis is unclear.

The roles of tryptophan metabolite indole-3-acetic acid (IAA) in inflammation and tumor development were investigated in dextran sodium sulfate (DSS) and azoxymethane (AOM)-DSS mouse models with or without IAA supplementation and with or without Lactobacillus reuteri-produced IAA. Pregnane X receptor (PXR) knockout (KO) mice and aryl hydrocarbon receptor KO mice were used to explore the mechanism by which IAA regulates interleukin (IL)-35 expression. IL-35+ immune cells were stimulated in vitro and analyzed by flow cytometry. Additionally, metabolites were analyzed by liquid chromatography-mass spectrometry.

We found that IAA, a metabolite of tryptophan produced in the gut by L. reuteri, can inhibit the development of colitis by inducing IL-35 expression in immunosuppressant cells. HuREG3αIECtg mice had high levels of intestinal microbiota-derived IAA, and these mice were resistant to AOM-DSS-induced cancer. Patients with colorectal cancer also had low peripheral blood levels of IAA. Further studies revealed that IAA-producing L. reuteri alleviated colitis symptoms and inhibited colon tumors by inducing macrophages, T cells, and B cells to produce IL-35. Finally, PXR KO completely abolished the effects of IAA on immune cells.

We demonstrate that gut microbiota-derived IAA can improve the precancerous colon inflammatory environment through IL-35, thereby inhibiting tumorigenesis, suggesting that IAA may be a preventive factor for colitis-related cancers.

Accurate data resources are essential for impactful medical research, but available structured datasets are often incomplete or inaccurate. Recent advances in open-weight large language models (LLMs) enable more accurate data extraction from unstructured text in electronic health records (EHRs) but have not yet been thoroughly validated for challenging diagnoses such as inflammatory bowel disease (IBD)-related neoplasia.

Create a validated approach using LLMs for identifying histopathologic diagnoses in pathology reports from the nationwide Veterans Health Administration database, including patients with genotype data within the Million Veteran Program (MVP) biobank.

Our approach utilizes simple 'yes/no' question prompts for following phenotypes of interest: any colorectal dysplasia, high-grade dysplasia and/or colorectal adenocarcinoma (HGD/CRC), and invasive CRC. We validated the method on diagnostic tasks by applying prompts to reports from patients with IBD (and validated separately in non-IBD) and calculated F-1 scores as a balanced accuracy measure.

In patients with IBD in MVP, we achieved F1-scores of 96.1% (95% CI 92.5-99.4%) for identifying dysplasia, 93.7% (88.2-98.4%) for identifying HGD/CRC, and 98% (96.3-99.4%) for identifying CRC. In patients without IBD in MVP, we achieved F1-scores of 99.2% (98.2-100%) for identifying any colorectal dysplasia, 96.5% (93.0-99.2%) for identifying HGD/CRC, and 95% (92.8-97.2%) for identifying CRC using LLM Gemma-2.

LLMs provided excellent accuracy in extracting the diagnoses of interest from EHRs. Our validated methods generalized to unstructured pathology notes, even withstanding challenges of resource-limited computing environments. This may therefore be a promising approach for other clinical phenotypes given the minimal human-led development required.

Microcapsules composed of synthetic polymeric matrices have attracted considerable attention in delivering oral probiotics. However, existing polymeric microcapsules demonstrate inadequate acid resistance and adaptability, as well as deficiency in the inflamed colon-specificity and uncontrolled release of probiotics therein. Herein, a DNA microcapsule is prepared as a probiotic-transporting micromotor through photo-crosslinking of hyaluronic acid methacrylate and acrydite-modified A-/C-rich oligomers within the microfludically generated droplets in the presence of nitric oxide-cleavable crosslinker and gas donor manganese carbonyl (MnCO). As the microcapsules traverse stomach, duodenum, and ultimately colon, the formation and dissociation of A-motif and i-motif structures instigate a reversible shrinking-swelling transition of microcapsules to preserve probiotic viability. Subsequently, the microcapsules exhibit chemotaxis towards inflamed colon site, driven by a gas-generating reaction between MnCO and elevated reactive oxygen species. Following disintegration of the microcapsules, triggered by endogenous nitric oxide, probiotics are released to reshape the dysbiosis of intestinal microflora. This advanced delivery system offers significant promise for the effective clinical management of inflammatory bowel disease.

Lactoferrin is an iron-binding glycoprotein that provides natural protective effects to the human body. Its biological properties, including antibacterial, antiviral, anti-inflammatory, immune-regulatory, and iron metabolism-regulating functions, have been extensively studied. With further research, lactoferrin's impact on tumorigenesis and tumor microenvironment has become increasingly evident, as it inhibits tumor proliferation, invasion, and metastasis through multiple pathways. This article summarizes the molecular mechanisms underlying lactoferrin's anticancer effects, explores its association with the malignant progression of various cancers, and highlights its clinical translational potential as a potential cancer biomarker and drug delivery carrier to enhance anticancer therapy efficiency. Due to the high safety profile of lactoferrin, its widespread application in the field of cancer treatment is highly anticipated.

Loss of SATB2 expression has emerged as a promising biomarker for dysplasia in inflammatory bowel disease (IBD), but its sensitivity and specificity remain unclear. We retrospectively evaluated immunohistochemical (IHC) staining of SATB2 and p53 in colorectal biopsies from 37 IBD patients (25 men and 12 women; median age: 48 years) with suspected dysplasia. The cohort included 26 ulcerative colitis (70%) and 11 Crohn's disease (30%). Fourteen patients (38%) developed IBD-associated invasive carcinoma, and 18 (49%) had persistent dysplasia on follow-up. Histologic review identified 80 lesions initially diagnosed as negative (16%), indefinite (39%), low-grade (36%), and high-grade (9%) dysplasia. IHC revealed aberrant p53 in 35 lesions (44%) and SATB2 loss in 42 lesions (53%), with 19 (24%) showing both abnormalities. Reappraisal of diagnoses combining histology and IHC reclassified lesions into indefinite (20%), low-grade (63%), and high-grade (17%) dysplasia. Lesions with SATB2 loss alone were more frequently of lower grade (P = .003). Dysplasia types included 15 conventional dysplasia (19%) and 65 nonconventional dysplasia (81%). The rates of p53 abnormality, SATB2 loss, and their combination were similar in nonconventional dysplasia (45%, 55%, and 75%, respectively) and conventional dysplasia (40%, 47%, and 67%, respectively) and comparable between cancer patients (50%, 56%, and 74%, respectively) and noncancer patients (39%, 50%, and 72%, respectively). Missed dysplasias in cancer patients were all nonconventional, and lesions with p53 abnormality more likely progressed to cancer (P = .002). In conclusion, SATB2 loss is a sensitive marker for IBD-associated dysplasia. Combined use of SATB2 and p53 IHC improves dysplasia detection and reduces false-negative diagnosis, supporting its application into routine diagnostic practice.

Autophagy plays a critical role in colitis-associated colorectal cancer (CAC). However, non-autonomous regulation of macroautophagic/autophagic flux during inflammation remains largely unexplored. Here, we show that F2rl1/Par2 deficiency (F2rl1[ΔIEC]) aggravated azoxymethane-dextran sulfate sodium-induced CAC based on tumor number and burden, promoted autophagy dysfunction characterized by SQSTM1/p62 accumulation and autophagosome-lysosome fusion inhibition in IECs, and reduced lysosomal acidification by suppressing FOXA2-induced V-ATPase ATP6V0E1 transcription. FOXA2 or ATP6V0E1 overexpression rescued autophagy impairment, reactive oxygen species accumulation, and DNA damage induced by F2RL1 deficiency in vitro and in vivo. Neutrophil-derived serine proteases suppressed FOXA2 expression, causing autophagy dysfunction. F2RL1 knockout completely blocked the effects of neutrophil proteases on FOXA2 and ATP6V0E1. The correlation between neutrophil and FOXA2-ATP6V0E1 activities was validated in ulcerative colitis and colorectal carcinoma. Therefore, F2RL1 deficiency in intestinal epithelial cells suppressed FOXA2 expression, leading to V-ATPase-mediated autophagic dysfunction and exacerbating CAC. Neutrophils may contribute to impaired autophagy and promote CAC by inactivating canonical F2RL1/PAR2 signaling via its derived proteases. F2RL1/PAR2 signaling may participate in maintaining intestinal homeostasis via autophagy. These findings provide useful insights into F2RL1/PAR2 and its cleaving serine proteases in CAC and would help in developing new therapeutic strategies for this malignancy.Abbreviations: AOM: azoxymethane; ATP6V0C: ATPase H+ transporting V0 subunit c; ATP6V0E1: ATPase H+ transporting V0 subunit e1; ATP6V1C2: ATPase H+ transporting V1 subunit C2; ATP6V1F: ATPase H+ transporting V1 subunit F; CAC: colitis-associated colorectal cancer; CRC: colorectal cancer; CTSB: cathepsin B; CTSG: cathepsin G; DEGs: differentially expressed genes; DSS: dextran sulfate sodium; FOXA2: forkhead box protein A2; F2RL1: F2R like trypsin receptor 1; IBD: inflammatory bowel disease; IECs: intestinal epithelial cells; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; ROS: reactive oxygen species; SQSTM1/p62: sequestosome 1; TFs: transcription factors; UC: ulcerative colitis.

Inflammatory bowel disease (IBD) is a complex chronic intestinal disorder in which excessive oxidative stress, dysregulated immune response, and microbiota dysbiosis contribute to recurrent episodes of inflammation in the colonic mucosa. Current clinical treatments focusing solely on inflammation resolution often exhibit limited efficacy due to the inability to fundamentally improve the pathological microenvironment. Herein, a probiotic membrane-modified drug delivery nanocomposite, namely, MPDA@Cur@EM, is developed for the comprehensive treatment of IBD. It contains two components: the curcumin-loaded mesoporous polydopamine nanoparticle (MPDA@Cur) as the core and the Escherichia coli Nissle 1917 outer membrane (EM) as the surface. For MPDA@Cur, the pathological microenvironment triggers the responsive release of curcumin. Importantly, MPDA@Cur can effectively alleviate the inflammatory response of LPS-activated macrophages through MPDA-mediated ROS scavenging and curcumin-induced M2 polarization. In the dextran sulfate sodium (DSS)-induced colitis model, the EM coating not only allows for the targeting enrichment of orally administered MPDA@Cur@EM to the inflamed colonic mucosa, but also participates in the regulation of intestinal flora. Consequently, MPDA@Cur@EM efficiently attenuates the inflammatory reaction and restores the intestinal barrier functions, demonstrated by the multipronged manner of restoring redox balance, remodeling immune homeostasis, and reshaping the gut microecology. Collectively, this work provides a safe and promising codelivery strategy of probiotic product, antioxidative nanoenzyme, and therapeutic drug for comprehensive management of IBD.

Several novel morphological variants of inflammatory bowel disease (IBD)- associated dysplasias have been described in recent years. The objective of our study was to reevaluate some of our IBD-associated neoplasia cases and retrospectively identify the so-called non-conventional dysplasias (NCDs).

We established a database of IBD patients registered between 2011 and 2015 at the Department of Pathology, University of Szeged. Patients with neoplastic samples were extracted into a separate database. Clinical and pathological characteristics were documented for each case. Histological slides were retrospectively reviewed, and cases were reclassified.

During the study period, 57 patients had neoplastic samples, and 47 patients were identified with conventional dysplasias (82.5%). A significant association was found between conventional dysplasias and dysplasia localization (P = 0.004), size (P = 0.012), endoscopic appearance (P = 0.006), grade (P = 0.011), macroscopic appearance of colorectal carcinoma (P = 0.009), and pT stage (P = 0.01). NCD was identified in 20 cases (35.1%). The most frequently observed subtype was serrated not otherwise specified (NOS) dysplasia (n = 6; 30%). Significant associations were detected between the development of NCD and several clinical-pathological features, including the occurrence (P < 0.001), localization (P = 0.001), size (P = 0.002), macroscopic appearance (P = 0.01), grade (P = 0.005), histological subtype (P = 0.003), pT (P = 0.003) and pM stage (P = 0.047) of colorectal carcinoma, as well as microsatellite status (P < 0.001).

The identification of IBD-associated NCDs might play a crucial role in future clinical practice. Some authors suggest closer patient follow-up upon identification of these lesions and recommend random biopsy sampling in IBD patients to detect potentially occult lesions. Further studies involving larger national and international patient cohorts are warranted to gain a more comprehensive understanding of the clinical behavior of NCDs.

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), is a chronic condition marked by persistent intestinal inflammation of unknown etiology. Disease onset involves genetic predisposition and environmental factors that disrupt the intestinal immune homeostasis. The intestinal microbiome and immune response play pivotal roles in disease progression. Advances in molecular therapies and early interventions have reduced surgery rates; however, colorectal cancer (CRC) remains a significant concern, driven by chronic inflammation. In UC, the risk of UC-associated neoplasia (UCAN) increases with disease duration, while CD patients face elevated risks of small intestine, anal fistula, and anal canal cancers. Endoscopic surveillance is advised for UCAN, but optimal screening intervals remain undefined, and no established guidelines exist for CD-associated cancers. UCAN morphology often complicates detection due to its flat, inflammation-blended appearance, which differs pathologically from sporadic CRC (sCRC). UCAN is frequently surrounded by dysplasia, with p53 mutations evident at the dysplasia stage. IBD-associated gastrointestinal cancers exemplify inflammation-driven carcinogenesis with distinct molecular mechanisms from the adenoma-carcinoma sequence. This review explores the epidemiology, risk factors, clinical and pathological features, current surveillance practices, and molecular pathways underlying inflammation-associated cancers in IBD.

Fusobacterium nucleatum (F. nucleatum) is an anaerobic bacterium known for its association with periodontal disease and oral infections. It has been implicated in the development of gastrointestinal diseases such as inflammatory bowel disease and colorectal cancer. Ulcerative colitis (UC), which is characterized by chronic inflammation of the colon, is a condition of unknown etiology with a rising incidence rate, significantly affecting the quality of life for patients. The increased intestinal permeability during UC may facilitate the adherence or invasion of F. nucleatum into the damaged intestinal barrier, leading to exacerbated inflammation.

This article introduces the concept of the oral-gut axis, reviewing existing literature to analyze the role of F. nucleatum in the pathogenesis of UC and exploring its potential pathogenic mechanisms. It also summarizes the latest advances in treating patients with UC who have F. nucleatum and looks forward to prospective therapeutic strategies and the translational prospects of F. nucleatum within the oral-gut axis.

F. nucleatum may be a key player in the pathogenesis of UC, likely due to its invasiveness during periods of increased intestinal permeability. The paper also discusses innovative approaches for the prevention and management of UC exacerbated by F. nucleatum, paving the way for more effective treatment of UC.

The review offers new insights into the complex relationship between the oral microbiome and intestinal diseases, enhancing our understanding of their dynamic interactions. There is a paucity of literature on therapeutic approaches, indicating a need for further clinical research.

The comprehension of intricate molecular mechanisms underlying how external stimuli promote malignancy is conducive to cancer early prevention. Esophageal squamous cell carcinoma (ESCC) is considered as an external stimuli (hot foods, tobacco, chemo-compounds) induced cancer, characterized by stepwise progression from hyperplasia, dysplasia, carcinoma in situ and invasive carcinoma. However, the underlying molecular mechanism governing the transition from normal epithelium to neoplastic processes in ESCC under persistent external stimuli has remained elusive. Herein, we show that a positive correlation between p38 and ERK1/2 activation during the progression of ESCC. We identify that phosphorylation of ACSL4 at T679 by p38 enhances its enzymatic activity, resulting in increased production of myristoyl-CoA (C14:0 CoA). This subsequently promotes Src myristoylation and activates downstream ERK signaling. Our results partially elucidate the role of ACSL4 in mediating stress-induced signaling pathways that activate growth cascades and contribute to tumorigenesis.

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the colon, often triggered by unhealthy diets, infections, and dysregulated immune responses. Current treatments for IBD are limited by relapse, drug resistance, side effects, and high costs. Glycine tabacina (Labill.) Benth, a legume native to southeastern China, has traditionally been used for its medicinal properties in treating rheumatoid arthritis, nephritis, and osteoporosis. However, its effects on IBD remain unexplored.

This study aimed to investigate the anti-colitis effects and underlying mechanisms of Glycine tabacina ethanol extract (GTE) using in vitro and in vivo models.

The chemical components of GTE were identified using high-performance liquid chromatography (HPLC). The effects of GTE on lipopolysaccharide (LPS)-induced inflammation and oxidative stress were assessed in Caco-2 cells. Dextran sulfate sodium (DSS)-induced colitis in mice was used to evaluate GTE's therapeutic potential. ELISA, RT-qPCR, immunofluorescence, and immunoblotting were performed to measure gene expression and signaling pathway activity. Histological analysis of colon tissues was conducted using H&E staining.

GTE significantly reduced LPS-induced inflammation and oxidative stress in Caco-2 cells and alleviated DSS-induced colitis in mice. Mechanistically, GTE decreased pro-inflammatory cytokines, matrix metalloproteinases (MMPs), and reactive oxygen species (ROS), while improving intestinal barrier integrity. Furthermore, GTE suppressed the NF-κB and MAPK/JNK pathways while activating the Nrf2 pathway. These results suggest that GTE may serve as a promising therapeutic agent for IBD by modulating key inflammatory and oxidative stress pathways.

The anti-inflammatory and antioxidant properties of GTE mitigated intestinal epithelial cell damage by preserving tight junction proteins and maintaining intestinal barrier integrity. Given its high efficacy and favorable safety profile, GTE represents a promising therapeutic candidate for managing chronic and refractory inflammatory disorders such as IBD.

Unmodifiable patient factors such as age, sex, and indication (case-mix) may influence colonoscopy performance. In this study, we explored how case-mix affected polyp detection, cecal intubation, and pain on a center level.

A cross-sectional study was performed on data from four centers in Western Norway registered in the national endoscopy quality registry, Gastronet, in 2020 and 2021. We extracted demographics, indication, and the performance measures cecal intubation rate (CIR), proportion of at least one polyp ≥ 5 mm in size per colonoscopy (PDR-5), and pain. We also analyzed the explanatory variables bowel preparation, withdrawal time, and sedation/analgesia.

First colonoscopies in 14,765 patients were included. Median age was 60 years (interquartile range 46-71) and 54% were women. Case-mix differed between centers and significantly influenced performance measures. Increased PDR-5 was associated with higher age and male sex (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.18-1.37). The indication surveillance had the highest PDR-5 (44.9%, 95% CI 42.6-47.1) and inflammatory bowel disease the lowest (14.6%, 95% CI 12.3-16.8). CIR decreased with increasing age. Men had less pain (OR 0.33, 95% CI 0.27-0.39). Among indications, surveillance and IBD had higher CIRs and less pain. Performance measures differed among centers, even after adjustment for case-mix and other known explanatory variables such as sedation/analgesia and bowel preparation.

Case-mix influenced performance measures. Although we showed center differences in performance, other factors, such as individual endoscopist skills, probably influence performance measures. Our study demonstrates the importance of considering case-mix when assessing colonoscopy performance.