Ulcerative colitis(UC) is a recurrent, chronic, nonspecific inflammatory bowel disease. The longer the course of the disease, the higher the risk of cancerization. In recent years, the incidence and mortality rates of colon cancer in China have been increasing year by year, seriously threatening the life and health of patients. Therefore, studying the mechanism of "inflammation cancer transformation" in UC and conducting early intervention is crucial. The "Kenang" theory is an important component of traditional Chinese medicine(TCM) theory of phlegm and blood stasis. It is based on the coexistence of phlegm and blood stasis in the body and deeply explores the pathogenic syndromes and characteristics of phlegm and blood stasis. Kenang is a pathological product formed when long-term Qi stagnation leads to the internal formation of phlegm and blood stasis, which is hidden deep within the body. It is characterized by being hidden, progressive, and difficult to treat. The etiology and pathogenesis of "inflammation cancer transformation" in UC are consistent with the connotation of the "Kenang" theory. The internal condition for the development of UC "inflammation cancer transformation" is the deficiency of healthy Qi, with Qi stagnation being the key pathological mechanism. Phlegm and blood stasis are the main pathogenic factors. Phlegm and blood stasis accumulate in the body over time and can produce cancer toxins. Due to the depletion of healthy Qi and a weakened constitution, the body is unable to limit the proliferation and invasion of cancer toxins, eventually leading to cancer transformation in UC. In clinical treatment, the focus should be on removing phlegm and blood stasis, with syndrome differentiation and treatment based on three basic principles: supporting healthy Qi to strengthen the body's foundation, resolving phlegm and blood stasis to break up the Kenang, and regulating Qi and blood to smooth the flow of energy and resolve stagnation. This approach helps to dismantle the Kenang, delay, block, or even reverse the cancerization process of UC, reduce the risk of "inflammation cancer transformation", improve the patient's quality of life, and provide new perspectives and strategies for early intervention in the development of colon cancer.
Humans ; Colitis, Ulcerative/immunology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Cell Transformation, Neoplastic

Colorectal cancer(CRC) is one of the most common malignant tumors worldwide, primarily originating from recurrent inflammatory bowel disease(IBD). Therefore, blocking the inflammation-cancer transformation in the colon has become a focus in the early prevention and treatment of CRC. The inflammation-cancer transformation in the colon involves multiple types of cells and complex pathological processes, including inflammatory responses and tumorigenesis. In this complex pathological process, immune cells(including non-specific and specific immune cells) and non-immune cells(such as tumor cells and fibroblasts) interact with each other, collectively promoting the progression of the disease. In traditional Chinese medicine(TCM), inflammation-cancer transformation in the colon belongs to the categories of dysentery and diarrhea, with the main pathogenesis being cold and heat in complexity. This paper first elaborates on the complex molecular mechanisms involved in the inflammation-cancer transformation process in the colon from the perspectives of inflammation, cancer, and their mutual influences. Subsequently, by comparing the pathogenic characteristics and clinical manifestations between inflammation-cancer transformation and the TCM pathogenesis of cold and heat in complexity, this paper explores the intrinsic connections between the two. Furthermore, based on the correlation between inflammation-cancer transformation in the colon and the TCM pathogenesis, this paper delves into the importance of the interaction between inflammation and cancer. Finally, it summarizes and discusses the clinical and basic research progress in the TCM intervention in the inflammation-cancer transformation process, providing a theoretical basis and treatment strategy for the treatment of CRC with integrated traditional Chinese and Western medicine.
Humans ; Colon/pathology* ; Integrative Medicine ; Animals ; Cold Temperature ; Cell Transformation, Neoplastic/drug effects* ; Medicine, Chinese Traditional ; Hot Temperature ; Inflammation ; Drugs, Chinese Herbal/therapeutic use* ; Colonic Neoplasms/drug therapy*

Gegen Qinlian Decoction(GQD) is a classic prescription for the clinical treatment of ulcerative colitis(UC). This study, based on the differences in efficacy observed in UC mice under different level of bile acids treated with GQD, aims to clarify the impact of bile acids on UC and its therapeutic effects. It further investigates the expression of bile acid receptors in the liver of UC mice, and preliminarily reveals the mechanism through which GQD affects bile acid synthesis in the treatment of UC. A UC mouse model was established using dextran sulfate sodium(DSS) induction. The efficacy of GQD was evaluated by assessing the general condition, disease activity index(DAI) score, colon length, and histopathological changes in colon tissue via hematoxylin and eosin(HE) staining. ELISA and Western blot were used to evaluate the inflammatory response in colon tissue. The total bile acid(TBA) level and liver damage were quantified using an automatic biochemistry analyzer. The expression levels of bile acid receptors and bile acid synthetases in liver tissue were detected by Western blot and RT-qPCR. The results showed that compared with the model group, GQD treatment significantly improved the DAI score, colon shortening, and histopathological damage in UC mice. The levels of pro-inflammatory factors TNF-α and IL-6 in the colon were significantly reduced. Serum TBA levels were significantly decreased, while alkaline phosphatase(ALP) levels significantly increased. After administration of cholic acid(CA), UC symptoms in the CA + GQD group were significantly aggravated compared with the GQD group. The DAI score, degree of weight loss, colon injury, serum TBA, and liver injury markers all increased significantly. However, compared with the CA group, the CA + GQD group showed a marked reduction in TBA levels and a significant improvement in UC-related symptoms, indicating that GQD can alleviate UC damage exacerbated by CA. Further investigation into the expression of bile acid receptors and synthetases in the liver showed that under GQD treatment, the expression of farnesoid X receptor(FXR) and small heterodimer partner(SHP) significantly increased, while the expression of G protein-coupled receptor 5(TGR5) and cholesterol 7α-hydroxylase(Cyp7A1) significantly decreased. These findings suggest that GQD may affect bile acid receptors and synthetases, inhibiting bile acid synthesis through the FXR/SHP pathway to treat UC.
Animals ; Colitis, Ulcerative/genetics* ; Bile Acids and Salts/biosynthesis* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Male ; Humans ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Colon/metabolism* ; Disease Models, Animal ; Liver/metabolism* ; Mice, Inbred C57BL

To study the therapeutic effect and mechanisms of ethyl syringate(MD) on ulcerative colitis(UC), the MTT assay was used to detect the proliferation inhibition of RAW264.7 cells and HT-29 cells by different concentrations of MD(50, 100, 200, 400 μmol·L~(-1)). UC cell models were constructed by inducing RAW264.7 cells and HT-29 cells with lipopolysaccharide(LPS) and tumor necrosis factor-α(TNF-α). An animal model was established by inducing mice with 2.5% dextran sulfate sodium(DSS) to verify the therapeutic effect of MD on UC. A control group, a model group(LPS or TNF-α), and groups treated with different concentrations of MD(50, 100, 200, 400 μmol·L~(-1)) were set up in this study. Nitric oxide(NO) levels were measured using a NO detection kit. Intracellular reactive oxygen species(ROS) levels were assessed using a laser confocal microscope and ROS kit. Enzyme-linked immunosorbent assay(ELISA) was used to detect changes in the levels of interleukin-6(IL-6), TNF-α, interferon-γ(INF-γ), interleukin-10(IL-10), and myeloperoxidase(MPO) in cells and animal tissues. Western blot was used to detect the expression levels of phosphorylated Janus kinase 2(p-JAK2), Janus kinase 2(JAK2), phosphorylated signal transducer and activator of transcription 3(p-STAT3), signal transducer and activator of transcription 3(STAT3), zonula occludens-1(ZO-1), occludin, and claudin-1 in cells and animal tissues. The results showed that MD can improve the inflammatory response by inhibiting the production of NO and ROS and regulating the expression of inflammatory factors. It significantly reduced the disease activity index(DAI) in mice, improved the shortening of the colon, and repaired intestinal epithelial damage by inhibiting the activation of the JAK2/STAT3 pathway, thereby exerting anti-UC activity.
Animals ; Colitis, Ulcerative/chemically induced* ; Janus Kinase 2/genetics* ; STAT3 Transcription Factor/genetics* ; Mice ; Humans ; Signal Transduction/drug effects* ; Male ; RAW 264.7 Cells ; Reactive Oxygen Species/metabolism* ; Nitric Oxide/metabolism* ; HT29 Cells ; Salicylates/administration & dosage* ; Protective Agents/administration & dosage*

This study investigated the therapeutic effects and mechanisms of Modified Yiyi Fuzi Baijiang Powder on ulcerative colitis(UC) in rats from the perspective of dampness. SD rats were randomly allocated into six groups(n=10): control, model, mesalazine, and Modified Yiyi Fuzi Baijiang Powder at low(3.96 g·kg~(-1)·d~(-1)), medium(7.92 g·kg~(-1)·d~(-1)), and high(15.84 g·kg~(-1)·d~(-1)) doses. UC was induced in all groups except the control by administration with 3% dextran sulfate sodium(DSS) solution for 7 days. The disease activity index(DAI) was recorded, and the colon tissue was collected for analysis. Histopathological changes were assessed by hematoxylin-eosin staining. Serum levels of D-lactic acid(D-LA) and diamine oxidase(DAO) were measured by ELISA. Immunohistochemistry and PCR were employed to evaluate the expression of aquaporins(AQP3, AQP4) and tight junction proteins [zonula occludens-1(ZO-1) and occludin] at both protein and mRNA levels. Compared with the control group, the model group showed an increased DAI scores(P<0.05), intestinal mucosal damage, elevated serum levels of DAO and D-LA(P<0.05), and decreased expression of AQP3, AQP4, ZO-1, and occludin(P<0.05). Treatment with Modified Yiyi Fuzi Baijiang Powder reduced the DAI scores(P<0.05), lowered the serum levels of D-LA and DAO(P<0.05), and upregulated the expression of AQP3, AQP4, ZO-1, and occludin at both protein and mRNA levels compared with the model group. These findings suggest that Modified Yiyi Fuzi Baijiang Powder exerts therapeutic effects on UC by reducing the intestinal mucosal permeability, promoting colonic mucosal repair, and regulating abnormal intestinal water metabolism, which may involve the upregulation of AQP3 and AQP4 expression.
Animals ; Colitis, Ulcerative/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Intestinal Mucosa/metabolism* ; Male ; Aquaporin 3/metabolism* ; Aquaporin 4/metabolism* ; Permeability/drug effects* ; Humans ; Powders ; Intestinal Barrier Function

To enhance the therapeutic efficacy of the baicalin-berberine complex(BA-BBR) in the treatment of ulcerative colitis(UC), BA-BBR nanocrystal microspheres(BA-BBR NC MS) were prepared using the dropping method. The microspheres were characterized in terms of morphology, particle size, differential scanning calorimetry(DSC), and powder X-ray diffraction(XRD). The release profiles of BA and BBR from the microspheres were measured, and the drug release mechanism was investigated. A rat model of UC was induced by 5% dextran sodium sulfate(DSS) and treated continuously for 7 days to evaluate the therapeutic effects of different formulations. The results showed that the prepared BA-BBR MS and BA-BBR NC MS were uniform gel spheres with particle sizes of(1.77±0.16) mm and(1.67±0.08) mm, respectively. After drying, the gels collapsed inward and exhibited a rough surface. During the preparation process, the BA-BBR nanocrystals(BA-BBR NC) were uniformly encapsulated within the microspheres. The release profiles of the microspheres followed a first-order kinetic model, and the 12-hour cumulative release of BA and BBR from BA-BBR NC MS was higher than that from BA-BBR MS. Compared with BA-BBR, BA-BBR NC, and BA-BBR MS, BA-BBR NC MS further alleviated UC symptoms in rats, most significantly reducing the levels of TNF-α, IL-1β, IL-6, and MPO, while increasing the level of IL-4 in colon tissues. These results indicate that BA-BBR NC MS, based on a "nano-in-micro" design, can deliver BA-BBR to the intestine and exert significant therapeutic effects in a UC rat model, suggesting it as a promising new strategy for the treatment of UC.
Animals ; Colitis, Ulcerative/metabolism* ; Rats ; Nanoparticles/chemistry* ; Microspheres ; Male ; Berberine/administration & dosage* ; Flavonoids/administration & dosage* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Particle Size ; Tumor Necrosis Factor-alpha/immunology* ; Drug Liberation ; Drug Compounding

Colorectal polyps are important early markers of colorectal cancer, and their early detection is crucial for cancer prevention. Although existing polyp segmentation models have achieved certain results, they still face challenges such as diverse polyp morphology, blurred boundaries, and insufficient feature extraction. To address these issues, this study proposes a parallel coordinate fusion network (PCFNet), aiming to improve the accuracy and robustness of polyp segmentation. PCFNet integrates parallel convolutional modules and a coordinate attention mechanism, enabling the preservation of global feature information while precisely capturing detailed features, thereby effectively segmenting polyps with complex boundaries. Experimental results on Kvasir-SEG and CVC-ClinicDB demonstrate the outstanding performance of PCFNet across multiple metrics. Specifically, on the Kvasir-SEG dataset, PCFNet achieved an F1-score of 0.897 4 and a mean intersection over union (mIoU) of 0.835 8; on the CVC-ClinicDB dataset, it attained an F1-score of 0.939 8 and an mIoU of 0.892 3. Compared with other methods, PCFNet shows significant improvements across all performance metrics, particularly in multi-scale feature fusion and spatial information capture, demonstrating its innovativeness. The proposed method provides a more reliable AI-assisted diagnostic tool for early colorectal cancer screening.
Humans ; Colonic Polyps/diagnostic imaging* ; Colorectal Neoplasms/diagnostic imaging* ; Neural Networks, Computer ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Early Detection of Cancer

Objective To generate and characterize natural killer cell (NK cell)-conditional Cd226 gene knockout mice using Cre-loxP technology, and to explore the role of CD226 on NK cells in alleviating intestinal inflammation in a murine model of ulcerative colitis (UC). Methods NK cell-conditional Cd226 gene knockout mice were generated by crossing loxP-flanked Cd226 mice with Ncr1-Cre mice via the Cre-loxP system. Polymerase chain reaction (PCR) and agarose gel electrophoresis were used for genotyping. A UC model was established by dextran sulfate sodium (DSS) induction. Flow cytometry was performed to analyze CD226 expression levels on NK cells and the infiltration of related immune cells in colon tissues. Hematoxylin-eosin (HE) staining was performed to assess the degree of colonic inflammation. Results DNA gel electrophoresis and flow cytometry confirmed the successful generation of NK cell-specific Cd226 knockout mice. After conditional knockout of Cd226 in NK cells, inflammation in the UC mouse model was alleviated. Flow cytometry results showed a reduced proportion of NK cells in peripheral blood and the colon lamina propria, while HE staining demonstrated attenuated inflammatory responses. Conclusion Specific knockout of Cd226 in NK cells mitigates intestinal inflammation in UC mice by reducing NK cell numbers and inhibiting their pro-inflammatory functions.
Animals ; Colitis, Ulcerative/pathology* ; Killer Cells, Natural/metabolism* ; Mice, Knockout ; T Lineage-Specific Activation Antigen 1 ; Antigens, Differentiation, T-Lymphocyte/genetics* ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Male

OBJECTIVE: To identify protein markers that may be associated with ulcerative colitis (UC) by analyzing differential proteins in the salivary exosomes from newly diagnosed patients with active UC and healthy controls (HC), and to investigate the function of salivary exosome-specific high-expression proteins in UC patients and their potential role in the pathogenesis of UC. METHODS: All patients and healthy controls were recruited from Peking University People' s Hospital. Whole saliva was obtained from 37 patients with newly diagnosed active ulcerative colitis (n=37) and apparently healthy controls (n=10). Salivary exosomes were extracted from samples, and the proteins within the exosomes were identified by liquid chromatograph-mass spectrometer (LC-MS/MS). The differentially expressed protein genes underwent gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis using the DAVID tool. In vitro, macrophages were co-cultured with salivary exosomes from UC group and those from HC group, respectively, and real-time quantitative polymerase chain reaction (qPCR) was used to detect levels of CD80⁺ and CD86⁺. Additionally, ELISA was performed to measure secretion levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) in the cell supernatant. RESULTS: A total of 259 proteins were co-expressed in saliva exosomes from UC group and HC group, among which 11 proteins were highly expressed in the UC group, including PDIA4, A2M, EEF2, C3, PSMA2, PSMB6, PSMA1, IGHG1, IGHG3, IGHG4 and SERPING1, while 4 proteins were lowly expressed in UC group, including TCN1, SLPI and SERPING. Functional analysis of these 15 proteins, along with 129 specific proteins found only in the UC patients and 69 specific proteins found only in HC patients, respectively, was conducted using GO/KEGG. The results revealed that in the UC group, proteasome-related proteins such as PSMA1, PSMA2 and PSMB6 expressions were increased in salivary exosomes while many key molecules involved in complement cascade pathways, such as C3 were up-regu-lated. In vitro co-culture experiments demonstrated that compared with healthy controls, the salivary exosomes of the UC patients in active stage could play a pro-inflammatory role by promoting the transformation of macrophages into M1 type cells that secrete inflammatory factors IL-1β, IL-6 and TNF-α. CONCLUSION Salivary exosomes in the UC patients may have the function of promoting inflammation. Analysis of protein levels in the saliva of the UC patients and healthy controls revealed significant differences in the expression levels of 15 co-expressed proteins between the two groups. Among them, C3, PSMA2, PSMB6 and PSMA1 were found to be mainly related to immune and inflammatory reactions in the UC group. These findings suggest that proteins with high specific expression in salivary exosomes of the UC patients have the potential to be used as a disease marker for UC diagnosis and may contribute to the pathogenesis of UC.
Humans ; Colitis, Ulcerative/metabolism* ; Exosomes/metabolism* ; Saliva/metabolism* ; Biomarkers/analysis* ; Male ; Female ; Adult ; Case-Control Studies ; Interleukin-6/metabolism* ; Middle Aged

OBJECTIVE: To explore the potential apoptotic mechanisms of 3 Morchella extracts (Morchella conica, Morchella esculenta and Morchella delicosa) on breast and colon cancer cell lines using apoptotic biomarkers. METHODS: Human breast cell line (MCF-7) and colon cancer cell line (SW-480) were treated with methanol and ethanol extracts of 3 Morchella species with concentration ranging from 0.0625 to 2 mg/mL. After that their effects on gene expression of apoptosis related markers (pro-apoptotic markers including Bax, caspase-3, caspase-7, and caspase-9, and the antiapoptotic marker including Bcl-2) were determined using reverse transcription polymerase chain reaction. RESULTS: All Morchella extracts reduced breast and colon cancer cells proliferation at half inhibitory concentration (IC₅₀) of 0.02 ±0.01 to 0.68 ±0.30 mg/mL. As expected, all Morchella extracts significantly increased gene expressions of Bax, caspase-3, caspase-7, and caspase-9 and downregulated the gene expression of Bcl-2 in MCF-7 and SW-480 cell lines (P<0.05). CONCLUSIONS Morchella extracts demonstrated significant anti-proliferative activity against breast and colon cancer cell lines via an apoptosis induction mechanism. Anticancer activity of Morchella extracts and activation of apoptosis in breast and colon cancer cells suggest that it may be used to develop chemotherapeutic agents against cancer in future.
Humans ; Apoptosis/genetics* ; Colonic Neoplasms/drug therapy* ; Breast Neoplasms/drug therapy* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Plant Extracts/pharmacology* ; Gene Expression Regulation, Neoplastic/drug effects* ; MCF-7 Cells ; Ascomycota/chemistry*