Of mice and men: murine bile acids explain species differences in the regulation of bile acid and cholesterol metabolism.

Compared with humans, rodents have higher synthesis of cholesterol and bile acids (BAs) and faster clearance and lower levels of serum LDL-cholesterol. Paradoxically, they increase BA synthesis in response to bile duct ligation (BDL). Another difference is the production of hydrophilic 6-hydroxylated muricholic acids (MCAs), which may antagonize the activation of FXRs, in rodents versus humans.

Gallbladder bile supersaturated with cholesterol in gallstone patients preferentially develops from shortage of bile acids.

Gallstone (GS) formation requires that bile is supersaturated with cholesterol, which is estimated by a cholesterol saturation index (CSI) calculated from gallbladder (GB) total lipids and the mol% (mole percent) of bile acids (BAs), cholesterol, and phospholipids (PLs). Whereas CSI indicates GS risk, we hypothesized that additional comparisons of GB lipid mol% data are inappropriate to identify why CSI is increased in GS disease. We anticipated that GB lipid mmol/l (millimole per liter) levels should instead identify that, and therefore retrieved GB mmol/l data for BAs, cholesterol, and PLs from a study on 145 GS and 87 GS-free patients and compared them with the corresponding mol% data.

SPION primes THP1 derived M2 macrophages towards M1-like macrophages.

Potentially, cellular iron regulates functional plasticity in macrophages yet; interaction of functionally polarized macrophages with iron-oxide nanoparticles has never been studied. We found that monocyte differentiation alters cellular ferritin and cathepsin L levels and induces functional polarization in macrophages. Iron in super paramagnetic iron-oxide nanoparticle (SPION) induces a phenotypic shift in THP1 derived M2 macrophages towards a high CD86+ and high TNF α+ macrophage subtype.

Fodipir and its dephosphorylated derivative dipyridoxyl ethyldiamine are involved in mangafodipir-mediated cytoprotection against 7β-hydroxycholesterol-induced cell death.

Objective: Mangafodipir exerts pharmacological effects, including vascular relaxation and protection against oxidative stress and cell death induced by oxysterols. Additionally, mangafodipir has been proposed for cardiovascular imaging. The primary metabolites of mangafodipir, manganese dipyridoxyl ethyldiamine (MnPLED) and its constituent dipyridoxyl diphosphate (Dp-dp) also known as fodipir, are pharmacologically active.

Cell death induced by 7-oxysterols via lysosomal and mitochondrial pathways is p53-dependent.

Oxysterol accumulation and p53 expression mainly in macrophages have been associated with cell death and necrotic core formation in human atheroma progression. Oxidative stress and lysosomal membrane permeabilization (LMP) in macrophages are important causes of macrophage apoptosis. However, it is not understood how p53 and oxysterols interact in the process.

Degradation of superparamagnetic iron oxide nanoparticle-induced ferritin by lysosomal cathepsins and related immune response.

Aim: To examine the physiological impact of superparamagnetic iron oxide nanoparticles (SPIONs) on cell function and its interaction with oxysterol laden cells.

Materials & Methods: Intracellular iron was determined by Prussian blue staining. Cellular ferritin, cathepsin L and ferroportin were analyzed by flow cytometry and fluorescence microscopy.

Lysosomal membrane permeabilization causes oxidative stress and ferritin induction in macrophages.

Moderate lysosomal membrane permeabilization (LMP) is an important inducer of apoptosis. Macrophages are professional scavengers and are rich in hydrolytic enzymes and iron. In the present study, we found that LMP by lysosomotropic detergent MSDH resulted in early up-regulation of lysosomal cathepsins, oxidative stress and ferritin up-regulation, and cell death.

Dimethyl sulfoxide prevents 7β-hydroxycholesterol-induced apoptosis by preserving lysosomes and mitochondria.

Dimethyl sulfoxide (DMSO) is a widely used vehicle for water-insoluble substances and exerts a wide range of pharmacologic effects including anti-inflammatory and free radical scavenging properties. Additionally, in an animal model, DMSO inhibited cholesterol-induced atherosclerosis. Despite such profound pharmacologic effects, mechanisms at the cellular level are not well understood.

Prevention of 7β-hydroxycholesterol-induced cell death by mangafodipir is mediated through lysosomal and mitochondrial pathways.

Mangafodipir, a MRI contrast agent, has been used as a viability marker in patients with myocardial infarction and showed vascular relaxation effect. It confers myocardial protection against oxidative stress. However mechanisms underlying such protection have not yet been investigated.