Identification of a Novel Substrate for eEF2K and the AURKA-SOX8 as the Related Pathway in TNBC.

Eukaryotic elongation factor 2 kinase (eEF2K) has been considered as a putative target for cancer therapy; however, the underlying mechanisms of eEF2K in triple-negative breast cancer (TNBC) progression remain to be fully elucidated. In this study, it is shown that eEF2K is highly expressed in TNBC and is associated with poor prognosis. In vitro, in vivo, and patient-derived organoid experiments demonstrate that knockdown of eEF2K significantly impedes progression of TNBC.

Structure-Activity Relationship Studies of Substituted 2-Phenyl-1,2,4-triazine-3,5(2,4)-dione Analogues: Development of Potent eEF2K Degraders against Triple-Negative Breast Cancer.

eEF2K, an atypical alpha-kinase, is responsible for regulating protein synthesis and energy homeostasis. Aberrant eEF2K function has been linked to various human cancers, including triple-negative breast cancer (TNBC). However, limited cellular activity of current eEF2K modulators impedes their clinical application.

Design and Characterization of a Novel eEF2K Degrader with Potent Therapeutic Efficacy Against Triple-Negative Breast Cancer.

Dysregulated eEF2K expression is implicated in the pathogenesis of many human cancers, including triple-negative breast cancer (TNBC), making it a plausible therapeutic target. However, specific eEF2K inhibitors with potent anti-cancer activity have not been available so far. Targeted protein degradation has emerged as a new strategy for drug discovery.

Identification and evaluation of a novel PARP1 inhibitor for the treatment of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a particularly invasive subtype of breast cancer and usually has a poor prognosis due to the lack of effective therapeutic targets. Approximately 25% of TNBC patients carry a breast cancer susceptibility gene1/2 (BRCA1/2) mutation. Clinically, PARP1 inhibitors have been approved for the treatment of patients with BRCA1/2-mutated breast cancer through the mechanism of synthetic lethality.

Myristica fragrans promotes ABCA1 expression and cholesterol efflux in THP-1-derived macrophages.

Myristica fragrans is a traditional herbal medicine and has been shown to alleviate the development of atherosclerosis. However, the anti-atherogenic mechanisms of M. fragrans are still to be addressed.

Artesunate inhibits atherosclerosis by upregulating vascular smooth muscle cells-derived LPL expression via the KLF2/NRF2/TCF7L2 pathway.

Lipoprotein lipase (LPL) plays a central role in hydrolyzing triglyceride and its deficiency leads to atherosclerosis. Artesunate (ART), a derivative of artemisinin, has been demonstrated that ART reduces the formation of atherosclerotic plaques. However, it remains unclear whether ART-alleviated atherosclerotic lesion is involved in regulating lipid metabolism.

Fargesin alleviates atherosclerosis by promoting reverse cholesterol transport and reducing inflammatory response.

Background And Aims: Fargesin mainly functions in the improvement of lipid metabolism and the inhibition of inflammation, but the role of fargesin in atherogenesis and the molecular mechanisms have not been defined. We aimed to explore if and how fargesin affects atherosclerosis by regulating lipid metabolism and inflammatory response.

Methods And Results: ApoE mice were fed a high-fat diet to form atherosclerotic plaques and then administrated with fargesin or saline via gavage.

Angiopoietin-1 aggravates atherosclerosis by inhibiting cholesterol efflux and promoting inflammatory response.

Objective: Angiopoietin-1 (Ang-1), a secreted protein, mainly regulates angiogenesis. Ang-1 has been shown to promote the development of atherosclerosis, whereas little is known about its effects on lipid metabolism and inflammation in this process.

Method: Ang-1 was transfected into ApoE mice via lentiviral vector or incubated with THP-1 derived macrophages.

CXCL12 promotes atherosclerosis by downregulating ABCA1 expression via the CXCR4/GSK3β/β-catenin/TCF21 pathway.

CXC chemokine ligand 12 (CXCL12) is a member of the CXC chemokine family and mainly acts on cell chemotaxis. CXCL12 also elicits a proatherogenic role, but the molecular mechanisms have not been fully defined yet. We aimed to reveal if and how CXCL12 promoted atherosclerosis via regulating lipid metabolism.

Pregnancy-associated plasma protein-A in atherosclerosis: Molecular marker, mechanistic insight, and therapeutic target.

Pregnancy-associated plasma protein-A (PAPP-A), a member of the metzincin metalloproteinase superfamily, can enhance local insulin-like growth factor (IGF) bioavailability through proteolytic cleavage of three IGF binding proteins. In patients with coronary atherosclerosis disease (CAD), elevated PAPP-A levels are significantly associated with a higher risk of cardiovascular events. Accumulating evidence indicates that this protease exerts a proatherogenic effect by altering a variety of pathological processes involved in atherosclerosis, including lipid accumulation, vascular inflammation, endothelial dysfunction, vascular smooth muscle cell proliferation and migration, plaque stability, and thrombus formation.

HDL impairs osteoclastogenesis and induces osteoclast apoptosis via upregulation of ABCG1 expression.

Cholesterol is one of the major components of biological membranes and has an important function in osteoclast formation and survival. It has been reported that high-density lipoprotein (HDL) promotes cholesterol efflux from osteoclasts and induces their apoptosis, but the underlying mechanisms are unclear. In this study, we investigated how HDL promotes osteoclast cholesterol efflux and explored its effect on osteoclast formation and survival.

Visceral adipose tissue-derived serine protease inhibitor accelerates cholesterol efflux by up-regulating ABCA1 expression via the NF-κB/miR-33a pathway in THP-1 macropahge-derived foam cells.

Atherosclerosis is a dyslipidemia disease characterized by foam cell formation driven by the accumulation of lipids. Visceral adipose tissue-derived serine protease inhibitor (vaspin) is known to suppress the development of atherosclerosis via its anti-inflammatory properties, but it is not yet known whether vaspin affects cholesterol efflux in THP-1 macrophage-derived foam cells. Here, we investigated the effects of vaspin on ABCA1 expression and cholesterol efflux, and further explored the underlying mechanism.