Targeted degradation of CDK4/6 by LA-CB1 inhibits EMT and suppresses tumor growth in orthotopic breast cancer.

Cyclin-dependent kinases 4 and 6 (CDK4/6) are central regulators of cell cycle progression and frequently dysregulated in cancers, including breast cancer. While selective CDK4/6 inhibitors like Palbociclib, Ribociclib, and Abemaciclib have shown clinical benefit in hormone receptor-positive (HR+) breast cancer, their efficacy is often limited by resistance mechanisms and dose-limiting toxicities. In this study, we developed LA-CB1, a novel Abemaciclib derivative that induces CDK4/6 degradation through the ubiquitin-proteasome pathway, aiming to achieve sustained inhibition of the CDK4/6-Rb axis.

[Relationship between macrophage pyroptosis and atherosclerosis based on theory of "spleen in correlation with endoplasmic reticulum"].

The key pathogenesis of atherosclerosis(AS) in traditional Chinese medicine(TCM) lies in the combination of phlegm and stasis due to spleen deficiency. In Western medicine, it is believed that pyroptosis can lead to atherosclerosis, and endoplasmic reticulum stress has been shown to promote pyroptosis. According to the theories of " spleen in correlation with endoplasmic reticulum",guided by spleen governing transportation and transformation, and endoplasmic reticulum processing proteins, it is believed that the syndrome of phlegm combined with stasis due to spleen deficiency has similarities with the mechanism of macrophage pyroptosis induced by endoplasmic reticulum stress in accelerating the progression of AS.

Jianpi Qutan Fang induces anti-atherosclerosis and ameliorates endothelial cell injury in high-fat diet ratsan anti-inflammatory and inhibiting Janus kinase/signal transducer and activator of transcription signaling pathway.

Objective: To investiage the possible mechanism underlying the effect of the Jianpi Qutan Fang (, JPQT) on Atherosclerosis (AS) which is the main pathological process of most cardiovascular diseases that affect millions of adults worldwide.

Methods: In the present study, rats were fed with a high-fat-diet (HFD) with vitamin D3 for 16 weeks and were orally administered atorvastatin treatment and different doses of JPQT. Histopathological changes and ultrastructural changes in the aorta were evaluated through hematoxylin-eosin staining and transmission electron microscopy (TEM), respectively.