Inflammation-responsive framework nucleic acids for ulcerative colitis therapy.

BACKGROUND Ulcerative colitis (UC) is a chronic inflammatory bowel disease for which effective therapies are lacking. Niu Huang (NH) is a traditional Chinese medicine used for inflammatory disorders. However, its protective effect on UC and its underlying mechanisms are unknown. AIM To uncover the mechanisms underlying the anti-colitis effects of the NH. METHODS Network pharmacology was applied to predict the active ingredients and targets of NH. Experimental validation was conducted in a dextran sulfate sodium-induced murine colitis model. The therapeutic efficacy was assessed using symptoms, histopathology, quantitative polymerase chain reaction, western blotting, immunohistochemistry and enzyme linked immunosorbent assay, while the underlying mechanism was investigated through integrated transcriptomic and proteomic analyses. In addition, the critical role of farnesoid X receptor (FXR) in mediating the effects of NH was validated using the FXR inhibitor guggulsterone and Fxr-/- mouse models. RESULTS Network pharmacology revealed that the bioactive component of NH is bile acid. Our animal experiments demonstrated that NH treatment significantly alleviated colitis symptoms and pathological damage. NH preserved intestinal mucosal integrity by upregulating occludin, claudin3, E-cadherin and leucine rich repeat containing G protein-coupled receptor 5 expression. Transcriptomic and proteomic analyses revealed that bile secretion, the nuclear factor kappa B signaling pathway and the complement and coagulation cascade pathway are key targets of NH. Western blotting confirmed that NH increased FXR levels and reduced P65, complement component 3 (C3) and NOD-like receptor family pyrin domain containing 3 (NLRP3) expression. Furthermore, experiments using Fxr -/- mice and the FXR antagonist revealed that FXR is a pivotal target through which NH attenuates UC. Mechanistic analysis revealed that the effects of NH on UC are mediated by the modulation of targets involved in the activation of FXR and the subsequent inhibition of C3/NLRP3 activation. CONCLUSION This study demonstrates the therapeutic effects of NH on UC. Mechanistically, NH acts by activating FXR, which subsequently inhibits the nuclear factor kappa B pathway to reduce C3 accumulation and suppress excessive NLRP3 inflammasome activation in colon tissue.

Mairin polarizes Macrophages into M2-phenotype and alleviates Ulcerative colitis through activating IRF4-CD5L pathway.

Dientamoeba fragilis dominance in IBS and Blastocystis sp. in ulcerative colitis.

Gynostemma pentaphyllum polysaccharides alleviate ulcerative colitis in mice via the Nrf2/ROS/NLRP3 axis and modulation of the gut microbiota.

Polysaccharide-based inflammatory microenvironment-responsive nanocarriers for ulcerative colitis: Advances in design, mechanisms, and therapeutic applications.

Mechanistic study of swertiamarin in treating ulcerative colitis by regulating YAP-mediated Wnt and Notch pathways for intestinal stem cell repair.

Association between spicy food consumption and inflammatory bowel disease: A case-control study from Saudi Arabia.

Xylo-oligosaccharide supplementation exacerbates colitis susceptibility in mice via taurine depletion.

Therapeutic effects of Pistacia terebinthus L. (Terebinth) fruit on ulcerative colitis: In vitro antioxidant and anti-inflammatory activities, in vivo histopathological-biochemical evaluation, and LC-HR/MS-based phenolic profiling.

Accurate evaluation of intestinal lesions and severity assessment of ulcerative colitis (UC) are crucial for therapeutic strategies and prognosis. This study aims to compare the efficacy of 18 F-FAPI and 18 F-FDG PET/CT in the evaluation of intestinal lesions and disease activity assessment of UC. This is a prospective cohort study, and patients with newly diagnosed or relapsed UC were enrolled. All participants underwent 18 F-FAPI PET/CT, 18 F-FDG PET/CT, abdominal contrast-enhanced CT, and colonoscopy within 1 week. Mayo Endoscopic Subscore (MES) was used as the reference standard for identification and severity assessment of intestinal lesions. Target-to-background ratio (TBR) of each segment in 18 F-FAPI/ 18 F-FDG PET/CT and global 18 F-FAPI/ 18 F-FDG PET/CT score were computed to represent the activity of independent segments and all segments, respectively. Before examinations, partial Mayo score was calculated based on clinical manifestations of patients, and levels of C-reactive protein, interleukin-6, erythrocyte sedimentation rate, platelet, and hemoglobin were determined. Finally, all data were analyzed to compare the efficacy of 18 F-FAPI and 18 F-FDG PET/CT in the evaluation of intestinal lesions and disease activity in UC. A total of 113 intestinal segments (including 90 lesion segments) were evaluated among 23 participants. Through receiver operating characteristic (ROC) analysis, 18 F-FAPI PET/CT showed significantly superior performance in detecting intestinal lesions compared with 18 F-FDG PET/CT ( P = 0.046) and abdominal contrast-enhanced CT ( P = 0.007). The correlations between FAPI-TBR and MES ( R2 = 0.75) and abdominal contrast-enhanced CT score ( R2 = 0.55) were stronger than those of FDG-TBR. 18 F-FAPI PET/CT showed superior discriminative capacity across different disease activity levels at both segmental ( P < 0.001) and patient-level ( P < 0.05) in intergroup comparison. The global 18 F-FAPI PET/CT score was significantly correlated with other activity indicators ( r = 0.49-0.76). Moreover, 18 F-FAPI PET/CT was also significantly superior to 18 F-FDG PET/CT ( P < 0.001) and abdominal contrast-enhanced CT ( P = 0.001) in detecting active lesions according to ROC analysis. The efficacy of 18 F-FAPI PET/CT in the evaluation of intestinal lesions and disease activity assessment of UC was superior to that of 18 F-FDG PET/CT. 18 F-FAPI PET/CT also correlated well with endoscopy, abdominal contrast-enhanced CT, clinical manifestations, and biomarkers. Therefore, 18 F-FAPI PET/CT may be a promising method for noninvasive assessment of disease activity of UC.

Curcumin alleviates murine ulcerative colitis by modulating Tfh-B cell crosstalk via the CD40/CD40L costimulatory pathway.

Ligilactobacillus murinus confers a dual benefit: Counteracting crotonis fructus-induced intestinal toxicity and synergizing with its processed form against ulcerative colitis.

Therapeutic mechanisms of natural plant polysaccharides in ulcerative colitis: A review.

Precise structural characterization and therapeutic potential of a glucomannan polysaccharide from dried rhizome of plant Bletilla striata against ulcerative colitis.

Design, synthesis and evaluation of shikimic acid derivatives for the treatment of ulcerative colitis.

Genomic Insights Into Inflammatory Bowel Disease in United States Hispanic Participants: An Ancestry-Focused Study.

Background: Colonoscopy is the gold standard for ulcerative colitis diagnosis. However, colonoscopy is invasive & often requires deep sedation & extensive preparation. The current study compared fecal calgranulin C versus fecal calprotectin in ulcerative colitis as a predictor of activity, compared to the invasive procedure of colonoscopy. Patient and Methods: 50 patients diagnosed with UC were involved in this study. They enrolled from the Gastroenterology Department. Patients with gastric malignancy, necrotizing enterocolitis, IBS & colonic cancer, or pregnant females were excluded. Results: Patients in the active group had significant anemia, higher WBCs, higher absolute neutrophilic count, lower lymphocytes %, lower serum albumin levels, higher CRP levels & higher ESR levels compared to those in the remission state. Patients in the active group had higher fecal calprotectin levels (630.18 μg/mg) & fecal Calgranulin C (689.32 μg/mg) levels in comparison to patients in the remission state (76.64 & 82.68 μg/mg), respectively. While there were statistically significant negative correlations between fecal calprotectin level & hemoglobin, lymphocytes %, monocytes % & serum albumin. There were statistically significant positive correlations between fecal Calgranulin C level & WBCs, absolute neutrophilic count, neutrophils %, NLR, CRP & ESR1. There was a highly statistically significant positive correlation between fecal Calgranulin C level & fecal calprotectin levels. Conclusion: Fecal Calgranulin C is more specific compared to other inflammatory markers in the prediction of Ulcerative colitis activity. Therefore, it is recommended to include it in the follow-up of UC patients.

Oyster peptides for relieving ulcerative colitis: A combination of cell experiments and network pharmacology screening

Cerium-based nanoplatforms inhibiting goblet cell-associated antigen passages to stabilize barrier function in ulcerative colitis.