Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Objective : To investigate the protective effect of obeticholic acid (OCA) on di(2⁃ethylhexyl) phthalate (DEHP)Ⅳinduced cholestasis in mice. Methods : Animal experiment 1 : Female ICR mice were randomly divided into 3 groups: the control group, DEHP low⁃dose group [50 mg/(kg d)]and DEHP high⁃dose group [200 mg/ ( kg d)] . All mice were administered with DEHP by gavage for 18 days. Animal experiment 2: Female ICR mice were randomly divided into 4 groups: the control group, OCA group, DEHP model group[200 mg/(kg ·d)] and DEHP + OCA group. All mice were administered with DEHP by gavage for 18 days and the duration of OCA was 12 - 18 days. Serum and liver tissues of mice were collected. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid ( TBA) levels, liver TBA levels, protein expression of farnesoid X receptor (FXR) and mRNA levels of FXR and SHP were detected. HE staining was used to observe the pathological changes in liver tissues. Results : Experiment 1: Compared with the control group, the liver weight, liver coefficient and the TBA concentrations in serum and liver significantly increased only in DEHP[200 mg/(kg ·d)] group(P < 0. 01), indicating that the modeling was successful. Animal experiment 2: Compared with the DEHP model group, the liver weight and liver coefficient significantly decreased after OCA treatment, and the TBA concentrations in serum and liver both decreased (P < 0. 01) .Compared with the control group, the protein expression level and its mRNA level of FXR decreased after DEHP[200 mg/(kg ·d)]treatment; Compared with the DEHP model group, the protein expression of FXR and the mRNA levels of FXR and SHP significantly increased after OCA treatment(P < 0. 05) . Conclusion DEHP exposure can induce cholestatic liver injury in mice, and OCA posttreatment has a protective effect on DEHP⁃induced cholestasis in mice.

Objective:To observe the effects of static 70° head-up tilted standing and of repeated body repositioning on hemodynamics in healthy young and middle-aged persons.Methods:The hemodynamics of 24 middle-aged and 23 younger persons were studied. Both groups were requested to perform static 70° head-up tilted standing and to repeatedly change their body position from 0° to 70° of tilt at a velocity of 1°/second for ten minutes in a random order. Before, between and after each test the subjects rested supine for ten minutes. Hemodynamic variables and blood pressure were recorded non-invasively.Results:The average heart rate (HR) increased significantly in both groups when rising from supine to the testing positions. In 70° tilted standing the average HR of the youth group, 84.0±9.5bpm, was significantly higher than that in the other position and that of the middle-aged group in the same position. The average HR of the middle-aged group in 70° tilted standing was also significantly higher than in the other position. Among the middle-aged group, the average stroke volume (SV) in the testing positions was significantly lower than when resting. Significant differences were observed in the average diastolic blood pressure (DBP) between the testing and rest positions for both groups, with the average DBP of the middle-aged group significantly higher than that of the youth group in all three positions. Among the youth group, the average SV, CO and systolic blood pressure (SBP) of the males were significantly higher than among the females in all of the different body positions.Conclusions:Young persons mainly rely on an increased heart rate to maintain cardiac output while middle-aged participants appear to achieve this through increased peripheral resistance. Repeated position changes have less impact on hemodynamics than 70° inclined standing, making it a safer and more stable training method. However, the long-term effects of such intervention need to be confirmed in further studies.