Baicalein ameliorates ulcerative colitis by improving intestinal epithelial barrier via AhR/IL-22 pathway in ILC3s.

Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract, which is closely related to gut barrier dysfunction. Emerging evidence shows that interleukin-22 (IL-22) derived from group 3 innate lymphoid cells (ILC3s) confers benefits on intestinal barrier, and IL-22 expression is controlled by aryl hydrocarbon receptor (AhR). Previous studies show that baicalein protects the colon from inflammatory damage. In this study we elucidated the molecular mechanisms underlying the protective effect of baicalein on intestinal barrier function in colitis mice. Mice were administered baicalein (10, 20, 40 mg·kg-1·d-1, i.g.) for 10 days; the mice freely drank 3% dextran sulfate sodium (DSS) on D1-D7 to induce colitis. We showed that baicalein administration simultaneously ameliorated gut inflammation, decreased intestinal permeability, restored tight junctions of colons possibly via promoting AhR/IL-22 pathway. Co-administration of AhR antagonist CH223191 (10 mg/kg, i.p.) partially blocked the therapeutic effects of baicalein in colitis mice, whereas AhR agonist FICZ (1 µg, i.p.) ameliorated symptoms and gut barrier function in colitis mice. In a murine lymphocyte line MNK-3, baicalein (5-20 µM) dose-dependently increased the expression of AhR downstream target protein CYP1A1, and enhanced IL-22 production through facilitating AhR nuclear translocation, these effects were greatly diminished in shAhR-MNK3 cells, suggesting that baicalein induced IL-22 production in AhR-dependent manner. To further clarify that, we constructed an in vitro system consisting of MNK-3 and Caco-2 cells, in which MNK-3 cell supernatant treated with baicalein could decrease FITC-dextran permeability and promoted the expression of tight junction proteins ZO-1 and occluding in Caco-2 cells. In conclusion, this study demonstrates that baicalein ameliorates colitis by improving intestinal epithelial barrier via AhR/IL-22 pathway in ILC3s, thus providing a potential therapy for UC.

Combined analysis of imaging tumor capsule with imaging tumor size guides the width of resection margin for solitary hepatocellular carcinoma.

BACKGROUND: The optimal width of resection margin (RM) for hepatocellular carcinoma (HCC) remains controversial. This study aimed to investigate the value of imaging tumor capsule (ITC) and imaging tumor size (ITS) in guiding RM width for patients with HCC. METHODS: Patients who underwent hepatectomy for HCC in our center were retrospectively reviewed. ITC (complete/incomplete) and ITS (≤ 3 cm/> 3 cm) were assessed by preoperative magnetic resonance imaging (MRI). Using subgroup analyses based on ITC and ITS, the impact of RM width [narrow RM (< 5 mm)/wide RM (≥ 5 mm)] on recurrence-free survival (RFS), overall survival (OS), and RM recurrence was analyzed. RESULTS: A total of 247 patients with solitary HCC were included. ITC and ITS were independent predictors for RFS and OS in the entire cohort. In patients with ITS ≤ 3 cm, neither ITC nor RM width showed a significant impact on prognosis, and the incidence of RM recurrence was comparable between the narrow RM and wide RM groups (15.6% vs. 4.3%, P = 0.337). In patients with ITS > 3 cm and complete ITC, the narrow RM group exhibited comparable RFS, OS, and incidence of RM recurrence with the wide RM group (P = 0.606, 0.916, and 0.649, respectively). However, in patients with ITS > 3 cm and incomplete ITC, the wide RM group showed better RFS and OS and a lower incidence of RM recurrence compared with the narrow RM group (P = 0.037, 0.018, and 0.046, respectively). CONCLUSIONS: As MRI-based preoperative markers, conjoint analysis of ITC with ITS aids in determining RM width for solitary HCC patients. Narrow RM is applicable in patients with ITS ≤ 3 cm regardless of ITC status and in those with ITS > 3 cm and complete ITC. Wide RM is preferred in those with ITS > 3 cm and incomplete ITC.

Dual-Energy CT for Patients Suspected of Having Liver Iron Overload: Can Virtual Iron Content Imaging Accurately Quantify Liver Iron Content?

PURPOSE: To prospectively assess the feasibility of using virtual iron content (VIC) imaging at dual-energy computed tomography (CT) to evaluate the liver iron content (LIC) in patients suspected of having liver iron overload and to compare the LIC grading performance of VIC imaging and magnetic resonance (MR) imaging. MATERIALS AND METHODS: This study was approved by the institutional review board, and informed consent was obtained from all patients. Fifty-six patients suspected of having liver iron overload (serum ferritin concentrations >500 µg/L) underwent unenhanced dual-energy CT and MR imaging of the liver. MR imaging-measured LICs were obtained in 34 of the 56 patients. VIC images were generated with dual-energy analysis. R2* and MR-measured LIC were obtained with gradient-echo and spin-echo sequences, respectively. Correlations between CT and MR measurements were analyzed. The diagnostic performance of VIC and R2* in the differentiation of different LIC thresholds were evaluated with receiver operating characteristic (ROC) analysis. RESULTS: Hepatic VIC showed significant correlation with R2* and MR-measured LIC (r = 0.885 and 0.871, respectively; P < .0001). To differentiate among different LIC thresholds of 1.8, 3.2, 7.0, and 15.0 mg of iron per gram of dry tissue, the corresponding optimal cutoff values for VIC were 2.50, 5.13, 8.93, and 17.97 HU, respectively. At a LIC threshold of 7.0 mg of iron per gram of dry tissue or higher, 100% sensitivity (15 of 15 patients) and 100% specificity (19 of 19 patients) were obtained for VIC. There was no significant difference between VIC and R2* (area under the ROC curve, 0.964 vs 0.993, respectively; P = .299) in grading LIC levels at a LIC threshold of 3.2 mg of iron per gram of dry tissue or higher. Conclusion Hepatic VIC is a potential index for accurately evaluating and grading clinically significant liver iron accumulation, with a diagnostic performance similar to that of MR imaging.

Virtual iron concentration imaging based on dual-energy CT for noninvasive quantification and grading of liver iron content: An iron overload rabbit model study.

OBJECTIVES: To assess the accuracy of liver iron content (LIC) quantification and grading ability associated with clinical LIC stratification using virtual iron concentration (VIC) imaging on dual-energy CT (DECT) in an iron overload rabbit model. METHODS: Fifty-one rabbits were prepared as iron-loaded models by intravenous injection of iron dextran. DECT was performed at 80 and 140 kVp. VIC images were derived from an iron-specific algorithm. Postmortem LIC assessments were conducted on an inductively coupled plasma (ICP) spectrometer. Correlation between VIC and LIC was analyzed. VIC were stratified according to the corresponding clinical LIC thresholds of 1.8, 3.2, 7.0, and 15.0 mg Fe/g. Diagnostic performance of stratification was evaluated by receiver operating characteristic analysis. RESULTS: VIC linearly correlated with LIC (r = 0.977, P < 0.01). No significant difference was observed between VIC-derived LICs and ICP (P > 0.05). For the four clinical LIC thresholds, the corresponding cutoff values of VIC were 19.6, 25.3, 36.9, and 61.5 HU, respectively. The highest sensitivity (100%) and specificity (100 %) were achieved at the threshold of 15.0 mg Fe/g. CONCLUSIONS: Virtual iron concentration imaging on DECT showed potential ability to accurately quantify and stratify hepatic iron accumulation in the iron overload rabbit model. KEY POINTS: • Virtual iron concentration (VIC) linearly correlates with liver iron content (LIC). • VIC accurately quantifies LIC. • VIC accurately grades LIC based on clinical LIC stratification.

A comparison of 3D-CTA and 4D-CE-MRA for the dynamic monitoring of angiogenesis in a rabbit VX2 tumor.

PURPOSE: To compare three-dimensional computed tomography angiography (3D-CTA) and four-dimensional contrast-enhanced magnetic resonance angiography (4D-CE-MRA) for the in vivo monitoring of tumor angiogenesis. MATERIALS AND METHODS: VX2 tumors were implanted into the right thigh muscle of 30 New Zealand white rabbits. The animals were randomly assigned to 5 groups, which, respectively, were scanned by 3D-CTA and 4D-CE-MRA on day 4, 7, 10, 13, or 16 after tumor implantation. After scanning, tumors were resected and processed for conventional histology and CD-31 immunohistochemistry. Tumor volume measurements derived from CT and MR imaging were compared with histopathological data. The minimum tumor diameter and the number of new tumor blood vessels detectable by 3D-CTA and 4D-CE-MRA were also compared. RESULTS: There were no significant differences in the tumor volume measurements derived from CT, MR, and histological analysis. The minimum diameter of tumor vessels detectable by 3D-CTA (0.68 ± 0.07 mm) was significantly less than that by 4D-CE-MRA (0.85 ± 0.12 mm) (P=0.005). The number of tumor vessels detected by each imaging method was not significantly different until day 13 after implantation, when 3D-CTA detected a greater number (P<0.001). The morphologic process of tumor angiogenesis was demonstrated dynamically by 3D-CTA and 4D-CE-MRA in vivo. CONCLUSIONS: Tumor angiogenesis can be dynamically monitored in vivo by 3D-CTA and 4D-CE-MRA. Of the two methods, 3D-CTA has better spatial resolution, but 4D-CE-MRA allows temporal resolution of tumor angiogenesis.

CTA combined with CT perfusion for assessing the efficacy of anti-angiogenic therapy in rabbit VX2 tumors.

RATIONALE AND OBJECTIVES: The aim of this study was to validate the feasibility of assessing the efficacy of antiangiogenic therapy on VX2 tumors using three-dimensional computed tomographic (CT) angiography (CTA) combined with CT perfusion. MATERIALS AND METHODS: Forty rabbits with VX2 tumors were randomly assigned to four groups according to different doses of antiangiogenic drug, which were administered intraperitoneally daily for 14 days. In each group, 10 animals were scanned using three-dimensional CTA and CT perfusion on days 1 and 2 after the latest administration of the drug. Tumor masses were sectioned, stained by immunohistochemistry, and processed for correlation between CT imaging and histology. RESULTS: The numbers of new tumor vessels from CTA were significantly different among the four groups (P < .001). As the dose of the drug increased, blood flow and blood volume on CT perfusion increased linearly, but the mean transit time and permeability surface-area product decreased linearly (P < .001). Immunohistochemical analyses showed that microvascular density decreased, while both luminal vascular number and mature vessel number increased linearly as the drug dose increased (P < .001). CT manifestations were correlated well with histologic findings (P < .05). CONCLUSIONS: It is feasible to assess the efficacy of antiangiogenic therapy on VX2 tumors using three-dimensional CTA combined with CT perfusion. Three-dimensional CTA can display the morphologic changes of tumor vessels, while CT perfusion can predict the functional changes of tumor vessels after antiangiogenic therapy.