Overview of bile acid signaling in the cardiovascular system

Bile acids(BAs)are classically known to play a vital role in the metabolism of lipids and in absorption.It is now well established that BAs act as signaling molecules,activating different receptors(such as farnesoid X receptor,vitamin D receptor,Takeda G-protein-coupled receptor 5,sphingosine-1-phosphate,muscarinic receptors,and big potassium channels)and participating in the regulation of energy homeostasis and lipid and glucose metabolism.In addition,increased BAs can impair cardiovascular function in liver cirrhosis.Approximately 50%of patients with cirrhosis develop cirrhotic cardiomyopathy.Exposure to high concentrations of hydrophobic BAs has been shown to be related to adverse effects with respect to vascular tension,endothelial function,arrhythmias,coronary atherosclerotic heart disease,and heart failure.The BAs in the serum BA pool have relevant through their hydrophobicity,and the lipophilic BAs are more harmful to the heart.Interestingly,ursodeoxycholic acid is a hydrophilic BA,and it is used as a therapeutic drug to reverse and protect the harmful cardiac effects caused by hydrophobic elevated BAs.In order to elucidate the mechanism of BAs and cardiovascular function,abundant experiments have been conducted in vitro and in vivo.The aim of this review was to explore the mechanism of BAs in the cardiovascular system.

Integrative Omics Uncovers Low Tumorous Magnesium Content as A Driver Factor of Colorectal Cancer

Magnesium(Mg)deficiency is associated with increased risk and malignancy in colorectal cancer(CRC),yet the underlying mechanisms remain elusive.Here,we used genomic,proteomic,and phosphoproteomic data to elucidate the impact of Mg deficiency on CRC.Genomic analysis identified 160 genes with higher mutation frequencies in Low-Mg tumors,including key driver genes such as KMT2C and ERBB3.Unexpectedly,initiation driver genes of CRC,such as TP53 and APC,displayed higher mutation frequencies in High-Mg tumors.Additionally,proteomic and phosphoproteomic data indicated that low Mg content in tumors may activate epithelial–mesenchymal transition(EMT)by modulating inflammation or remodeling the phosphoproteome of cancer cells.Notably,we observed a negative correlation between the phosphorylation of DBN1 at S142(DBN1S142p)and Mg content.A mutation in S142 to D(DBN1S142D)mimicking DBN1S142p up-regulated MMP2 and enhanced cell migration,while treatment with MgCl2 reduced DBN1S142p,thereby reversing this phenotype.Mechanistically,Mg2þattenuated the DBN1–ACTN4 interaction by decreasing DBN1S142p,which in turn enhanced the binding of ACTN4 to F-actin and promoted F-actin polymerization,ultimately reducing MMP2 expression.These findings shed new light on the crucial role of Mg deficiency in CRC progression and suggest that Mg supplementation may be a promising preventive and therapeutic strategy for CRC.