Tokushima Bunri University

Gastric ulcers are a major gastrointestinal disorder influenced by environmental and lifestyle factors, warranting for the discovery of effective therapeutic alternatives. Deverra tortuosa (Desf.) DC., a traditional medicinal plant, has demonstrated potential gastroprotective properties. This study assesses the anti-ulcerative effects of phenolic-rich ethanolic extract of D. tortuosa (DT-ETOH) against ethanol-induced gastritis in rats, alongside its underlying mechanisms of action. Comprehensive metabolites profiling via UHPLC-ESI-qTOF-MS/MS identified 35 bioactive compounds, primarily flavonoids and phenolic acids, along with coumarins, sterols, and fatty acids. Oral administration of DT-ETOH significantly mitigated gastric ulceration by reducing the ulcer index and oxidative stress markers, enhancing antioxidant enzyme activity (SOD, GSH), and modulating key inflammatory mediators (TNF-α, IL-6). Notably, DT-ETOH administration led to the upregulation of Keap-1 and HO-1 expression, increased iKba levels, and suppression of iNOS, indicating its role in oxidative stress regulation and inflammation suppression. Histopathological findings further confirmed the protective effects of DT-ETOH, demonstrating improved gastric mucosal integrity. These results provide evidence of DT-ETOH's gastroprotective, antioxidant, and anti-inflammatory properties, supporting its potential as a natural agent for gastric ulcer management.

This study evaluated whether temporal changes from the dynamic late phase to the hepatobiliary phase using gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid supported liver tumor classification. A total of 147 patients with 165 lesions (hepatocellular carcinoma [HCC], metastases, and hemangiomas) underwent 3.0 T MRI. Quantitative liver lesion contrast (Q-LLC) and its rate of change (%) at 3, 10, and 15 min postcontrast were analyzed. Tumors were stratified according to albumin-bilirubin (ALBI) grade. For ALBI grade 1, the Q-LLC significantly differed at 3 min and 10 min (P < 0.05). Q-LLC increased over time, and the rate of change was the lowest in HCC, followed by metastases, and was the highest in hemangiomas. Significant differences in the rate of change were observed among tumor types for ALBI grade 1 (P < 0.01). These findings suggest that the Q-LLC rate of change may aid in liver tumor classification, particularly in patients with preserved liver function.

Liver X receptors (LXRα and LXRβ) are nuclear receptors critical for lipid homeostasis and inflammation regulation, making them potential therapeutic targets for atherosclerosis and inflammatory diseases. While LXR agonists hold promise, their use is limited by adverse effects on hepatic lipogenesis. Riccardin C (RC) has shown promise as an LXRα partial agonist/ LXRβ antagonist with cell-type-selective properties. This study investigates the molecular mechanisms behind RC-induced LXRα activation. A series of LXRα/β chimera and point-mutated receptors was generated to identify the domains and residues required for RC-induced transactivation. Functional analysis revealed that mutating alanine-327 of LXRα to LXRβ-type histidine in helix 6 impaired RC-induced association with coactivator peptides, reducing transactivation. Conversely, mutating histidine-341 of LXRβ or the inactive chimera to the LXRα-type alanine partially restored the response to RC, highlighting the significance of the A327H mutation in selective LXRα activation by RC. Furthermore, in vivo experiments revealed that when administered orally to mice, RC selectively induced hepatic and intestinal Abca1 expression without stimulating hepatic lipogenic gene expression, thereby elevating HDL levels without increasing plasma and hepatic triglycerides. These findings offer valuable insights for the development of novel therapeutic agents.