Fucogalactan Sulfate (FS) from Laminaria japonica Regulates Lipid Metabolism in Diet-Induced Humanized Dyslipidemia Mice via an Intestinal FXR-FGF19-CYP7A1/CYP8B1 Pathway.

Our previous study found that fucogalactan sulfate (FS) from Laminaria japonica exhibited significant hypolipidemic effects. To further elucidate the mechanism, we first constructed a dyslipidemia mouse model with humanized gut microbiota and proved the main differential metabolic pathway involved bile acid metabolism. Then, we evaluated the beneficial effects of FS on dyslipidemia in this model mice, which revealed that oral FS administration reduced serum cholesterol levels and mitigated liver fat accumulation. Gut microbiota and microbiome analysis showed FS increased the abundance of Ruminococcaceae_NK4A214_group, GCA-900066755, and Eubacterium, which were positively associated with the fecal DCA, ß-MCA, and HDCA. Further investigation demonstrated that FS inhibited the hepatic farnesoid X receptor (FXR), while activating the intestinal FXR-FGF19 pathway, leading to suppression of CYP7A1 and CYP8B1, as well as potentially reduced bile acid synthesis and lipid absorption. Overall, FS regulated lipid metabolism in diet-induced humanized dyslipidemia mice via the bile acid-mediated intestinal FXR-FGF19-CYP7A1/CYP8B1 pathway.

Analysis of the amplitude changes and baseline shifts of respiratory motion using intra-fractional CBCT in liver stereotactic body radiation therapy.

PURPOSE: Using intra-fractional cone-beam CT (CBCT) to evaluate the amplitude changes and baseline shifts of respiratory motion in liver stereotactic body radiation therapy (SBRT). METHODS: The amplitude changes and baseline shifts of respiratory motion for 24 liver patients were evaluated by the four-dimensional (4D) CT, inter- and intra-fractional CBCT. The difference of the average liver position errors among all treatment fractions and the 4D CT representthe baseline shifts. According to the baseline shifts, the ITV to PTV margin was recalculated and the plan was re-designed to compare the dosimetric variation. RESULTS: The systematic and random errors of the baseline shifts for intra-fractional CBCT in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions were 0.99/1.60 mm, 2.03/2.46 mm, and 1.02/2.07 mm, respectively. The new ITV to PTV margins should be 4.0 mm, 7.0 mm, and 4.0 mm, respectively. The amplitude change of motion between the 4D CT and the intra-fractional CBCT was 1.03 ± 4.35 mm, with 31% of fractions exceeding 5 mm. To achieve the same dose coverage of the new PTV, the Dmean, V50, V40, V30, V25 of normal liver and maximum dose of the duodenum were significantly different. CONCLUSIONS: Significant amplitude changes and baseline shifts of motion occurred during dose delivery compared with those in 4D CT. Using the ITV to PTV margin of 4.0 mm (LR), 7.0 mm (SI), and 4.0 mm (AP) can ensure the target dose coverage and keep the dose constrain of normal tissues at an acceptable level.