Endothelial-to-mesenchymal transition (EndMT) plays significant roles in atherosclerosis, but the regulatory mechanisms involving lncRNAs remain to be elucidated. Here we sort to identify the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in ox-LDL-induced EndMT. The atherosclerosis model was established by feeding ApoE−/− mice with high-fat diet, and the levels of lncRNA MALAT1 in mouse arterial tissue were detected by RT-qPCR. Cell model was established by treating human umbilical vein endothelial cells (HUVECs) with ox-LDL, and the levels of EndMT markers, such as CD31, vWF, α-SMA and Vimentin and lncRNA MALAT1 levels were detected and their correlations were analyzed. The role of MALAT1 in EndMT and its dependence on Wnt/β-catenin signaling pathway was further detected by knocking down or overexpressing MALAT1. MALAT1 was upregulated in high-fat food fed ApoE−/− mice. HUVECs treated with ox-LDL showed a significant decrease in expression of CD31 and vWF, a significant increase in expression of α-SMA and vimentin, and upregulated MALAT1. An increased MALAT1 level facilitated the nuclear translocation of β-catenin induced by ox-LDL. Inhibition of MALAT1 expression reversed nuclear translocation of β-catenin and EndMT. Moreover, overexpression of MALAT1 enhanced the effects of ox-LDL on HUVEC EndMT and Wnt/β-catenin signaling activation. Our study revealed that the pathological EndMT required the activation of the MALAT1-dependent Wnt/β-catenin signaling pathway, which may be important for the onset of atherosclerosis. Not applicable.

Alzheimer's disease (AD) is the most common and severe degenerative disorder of the central nervous system in the elderly, profoundly impacting patients' quality of life. However, effective therapeutic agents for AD are still lacking. Bazi Bushen capsule (BZBS) is a traditional Chinese herbal compound with potential neuroprotective effects, yet its underlying mechanisms remain poorly understood. In this study, we utilized APP/PS1 transgenic mice to assess the therapeutic efficacy of BZBS. Initially, we evaluated the spatial learning and memory of the mice using the Barnes maze. The brain microcirculation was assessed through a small-animal ultrasound system, two-photon in vivo imaging, and micro-computed tomography angiography. Molecular, biochemical, and pathological analyses were conducted on brain tissues. Through network pharmacology, we identified potential intervention pathways and targets for BZBS in the treatment of AD, which we subsequently validated both in vivo and in vitro. Additionally, we employed molecular virtual docking screening and biolayer interferometry to elucidate the direct interactions of ginsenoside Rg5 and ginsenoside Ro in BZBS with AMPK and LKB1 proteins. The BZBS intervention significantly enhanced spatial learning and memory in APP/PS1 mice while decreasing Aβ deposition. Furthermore, BZBS protected cerebrovascular homeostasis and mitigated neuroinflammation, as evidenced by decreased blood-brain barrier permeability, increased expression of tight-junction proteins, and restored cerebral blood flow. Mechanistically, ginsenosides Rg5 and Ro in BZBS directly bind to AMPK and LKB1 proteins, activating the LKB1-AMPK-SIRT1 signaling pathway, promoting autophagy and mitochondrial autophagy, and alleviating oxidative stress damage in endothelial cells. BZBS enhances autophagy-related activity, decreases Aβ deposition, and improves endothelial cell homeostasis through the activation of the LKB1-AMPK-SIRT1 signaling pathway, ultimately leading to improved cognitive function in mice with AD. This study highlights the importance of enhancing autophagic activity and maintaining cerebrovascular homeostasis in mitigating cognitive decline in AD, providing evidence and new insights into the application of compound medicines for treating age-related neurological disorders.