Inhibition of RIPK1 alleviating vascular smooth muscle cells osteogenic transdifferentiation via Runx2.

Vascular calcification (VC) is recognized as a crucial risk factor for cardiovascular diseases. Our previous report revealed that the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) plays a role in this process. However, the underlying molecular mechanisms remain elusive. Notably, receptor-interacting protein kinase 1 (RIPK1) has been implicated in the development of cardiovascular diseases, yet its role and mechanisms in VC remain unexplored. To address this gap, we established models using chronic kidney disease mice and calcifying VSMCs to investigate the impact of RIPK1 on VC. Subsequently, a RIPK1-specific inhibitor (NEC-1) was applied in both in vitro and in vivo models. Our findings indicate significant activation of RIPK1 in calcified human arterial tissue, as well as in animal and cellular models. RIPK1 activation promotes the osteogenic transdifferentiation of VSMCs. Treatment with the NEC-1 substantially reduced VC. These results demonstrate that RIPK1 is a target for preventing VC.

Dietary antioxidants and vascular calcification: From pharmacological mechanisms to challenges.

Vascular calcification (VC), an actively regulated process, has been recognized as an independent and strong predictor of cardiovascular disease (CVD) and mortality worldwide. Diet has been shown to have a major role in the progression of VC. Oxidative stress (OS), a common pro-calcification factor, is closely related to VC, and evidence strongly suggests that dietary antioxidants directly prevent VC. Herein, we provided an overview of OS and its key role in VC and underlined the mechanisms of harmful effects of OS on VC. Furthermore, we introduced dietary antioxidants, and discussed about surrounding the challenges of dietary antioxidants in VC management. This review will benefit future research about the effects of dietary antioxidants on cardiovascular health.

Inhibition of invadopodia formation by diosgenin in tumor cells.

Diosgenin is a type of steroid extracted from the rhizome of Dioscorea plants. In traditional Chinese medicine, Dioscorea has the effect of 'eliminating phlegm, promoting digestion, relaxing tendons, promoting blood circulation and inhibiting malaria'. Recent studies have confirmed that diosgenin exhibits a number of pharmacological effects, including antitumor activities. Through its antitumor effect, diosgenin is able to block tumor progression and increase the survival rate of patients with cancer; ultimately improving their quality of life. However, the mechanism underlying its pharmacological action remains unclear. Once tumor cells reach a metastatic phase, it can be fatal. Increased migration and invasiveness are the hallmarks of metastatic tumor cells. Invadopodia formation is key to maintaining the high migration and invasive ability of tumor cells. Invadopodia are a type of membrane structure process rich in filamentous-actin and are common in highly invasive tumor cells. In addition to actin, numerous actin regulators, including cortical actin-binding protein (Cortactin), accumulate in invadopodia. Cortactin is a microfilament actin-binding protein with special repetitive domains that are directly involved in the formation of the cortical microfilament actin cell skeleton. Cortactin is also one of the main substrates of intracellular Src-type tyrosine protein kinases and represents a highly conserved family of intracellular cortical signaling proteins. In recent years, great progress has been made in understanding the role of Cortactin and its molecular mechanism in cell motility. However, the diosgenin-Cortactin-invadopodia mechanism is still under investigation. Therefore, the present review focused on the current research on the regulation of invadopodia by diosgenin via Cortactin.