1.IMM-H007 promotes hepatic cholesterol and triglyceride metabolism by activating AMPKα to attenuate hypercholesterolemia.
Jiaqi LI ; Mingchao WANG ; Kai QU ; Yuyao SUN ; Zequn YIN ; Na DONG ; Xin SUN ; Yitong XU ; Liang CHEN ; Shuang ZHANG ; Xunde XIAN ; Suowen XU ; Likun MA ; Yajun DUAN ; Haibo ZHU
Acta Pharmaceutica Sinica B 2025;15(8):4047-4063
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.
2.A NMRI SUCKLING MOUSE MODEL FOR THE EVALUATION OF INFECTIVITY OF CRYPTOSPORIDIUM PARVUM OOCYSTS
Chinese Journal of Parasitology and Parasitic Diseases 2000;18(2):94-96
[Objective] To evaluate the infectivity of Cryptosporidium parvum oocysts in NMRI suckling mouse.[Methods] Four-day- old SPF NMRI suckling mice were inoculated with different amounts of oocysts by oral gavage.On clay 7 after inoculation, suckling mice were sacrificed, and a suspension was prepared by homogenizing the intestinal tract from pylorus to anus. A mouse was considered infected when oocysts were found in smears of the intestinal content suspension stained with carbo lfuchsin solution. The infectivity of oocysts was evaluated as measured by the percentage of infected mice in each group. [Results] Mice receiving 1 500 or 2 000 oocysts were all infected. The percentages of infected mice were 88, 74, 51 and 28 respectively after ingestion of 1 000, 500, 250 and 100 oocysts. The percentage of infected mice was 9.5 % after ingesting as few as 50 oocysts. [Conclusion] This model is convenient for evaluation of the infectivity of C. parvum oocysts.

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