Noble metal-free bifunctional oxygen evolution and oxygen reduction acidic media electro-catalysts.

Identification of low cost, highly active, durable completely noble metal-free electro-catalyst for oxygen reduction reaction (ORR) in proton exchange membrane (PEM) fuel cells, oxygen evolution reaction (OER) in PEM based water electrolysis and metal air batteries remains one of the major unfulfilled scientific and technological challenges of PEM based acid mediated electro-catalysts. In contrast, several non-noble metals based electro-catalysts have been identified for alkaline and neutral medium water electrolysis and fuel cells. Herein we report for the very first time, F doped Cu1.

Chronic activation of FXR in transgenic mice caused perinatal toxicity and sensitized mice to cholesterol toxicity.

The nuclear receptor farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4, or NR1H4) is highly expressed in the liver and intestine. Previous reports have suggested beneficial functions of FXR in the homeostasis of bile acids, lipids, and glucose, as well as in promoting liver regeneration and inhibiting carcinogenesis. To investigate the effect of chronic FXR activation in vivo, we generated transgenic mice that conditionally and tissue specifically express the activated form of FXR in the liver and intestine.

Roles of microRNA-29a in the antifibrotic effect of farnesoid X receptor in hepatic stellate cells.

Liver fibrosis is a chronic disorder that is characterized by an alteration of the balance between fibrogenesis and fibrinolysis, which results in accumulation of excessive amounts of extracellular matrix (ECM) and distortion of the normal liver architecture. The activation and transformation of quiescent hepatic stellate cells (HSCs) into myofibroblast-like cells constitute a major mechanism for the increased production of ECM in the liver. The nuclear receptor farnesoid X receptor (FXR) shows potent antifibrotic activity in HSCs and protects animals in rodent models of liver fibrosis.

Inhibition of endothelin-1-mediated contraction of hepatic stellate cells by FXR ligand.

Activation of hepatic stellate cells (HSCs) plays an important role in the development of cirrhosis through the increased production of collagen and the enhanced contractile response to vasoactive mediators such as endothelin-1 (ET-1). The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is highly expressed in liver, kidneys, adrenals, and intestine. FXR is also expressed in HSCs and activation of FXR in HSCs is associated with significant decreases in collagen production.

Upregulation of scavenger receptor class B type I expression by activation of FXR in hepatocyte.

Objective: The farnesoid X receptor (FXR), a member of the nuclear receptor superfamily, has been proposed to play an important role in the pathogenesis of cardiovascular diseases by regulating the metabolism and transport of cholesterol and triglyceride. Scavenger receptor class B type I (SR-BI), a high-density lipoprotein receptor, plays an important role in decreasing lipid metabolism-associated cardiovascular diseases by regulating reverse cholesterol transport. Recent studies have shown that SR-BI expression is upregulated by several nuclear receptors.

A functional cross-talk between liver X receptor-α and constitutive androstane receptor links lipogenesis and xenobiotic responses.

The liver X receptor (LXR) and constitutive androstane receptor (CAR) are two nuclear receptors postulated to have distinct functions. LXR is a sterol sensor that promotes lipogenesis, whereas CAR is a xenosensor that controls xenobiotic responses. Here, we show that LXRα and CAR are functionally related in vivo.

Coordinated regulation of dimethylarginine dimethylaminohydrolase-1 and cationic amino acid transporter-1 by farnesoid X receptor in mouse liver and kidney and its implication in the control of blood levels of asymmetric dimethylarginine.

Asymmetric dimethylarginine (ADMA) is a potent endogenous inhibitor of endothelial nitric-oxide synthase (eNOS), and increased plasma concentrations of ADMA have been regarded as a risk factor for a number of cardiovascular diseases. Circulating ADMA is largely taken up by liver and kidney via system y(+) carriers of the cationic amino acid (CAT) family and subsequently metabolized by dimethylarginine dimethylaminohydrolases (DDAHs). As such, agents targeted at enhancing ADMA metabolism may prove to be useful in the prevention and/or treatment of various types of cardiovascular disease.

Polyhydroxylalkyleneamines: a class of hydrophilic cationic polymer-based gene transfer agents.

A new series of cationic polymers, poly[N,N-bis-(2-hydroxylpropyl) alkylalcoholamine-co-ethylenediamine] were synthesized by directly cross-linking several dichloro alkylating agents with ethylenediamine and its derivatives. Co-polymerization with cystamine introduces biodegradable disulfide bonds to the polymer backbone. When tested on COS-1 cells, PHAs showed reduced cytotoxicity, broad polymer to DNA ratios, and enhanced transfection activity that was 2-9-fold better than that of polyethylenimine.

Targeted delivery of nucleic-acid-based therapeutics to the pulmonary circulation.

Targeted delivery of functional nucleic acids (genes and oligonucleotides) to pulmonary endothelium may become a novel therapy for the treatment of various types of lung diseases. It may also provide a new research tool to study the functions and regulation of novel genes in pulmonary endothelium. Its success is largely dependent on the development of a vehicle that is capable of efficient pulmonary delivery with minimal toxicity.

Upregulation of decorin by FXR in vascular smooth muscle cells.

Decorin is a member of the family of small leucine-rich proteoglycans that are present in blood vessels and synthesized by vascular smooth muscle cells (VSMCs). Decorin plays complex roles in both normal vascular physiology and the pathogenesis of various types of vascular disorders. However, the mechanisms of regulation of decorin expression in vasculature are not clearly understood.

Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPARgamma in promoting steatosis.

Background & Aims: Liver X receptor (LXR) is known to promote hepatic lipogenesis by activating the lipogenic transcriptional factor sterol regulatory element-binding protein (Srebp). Pregnane X receptor (PXR), a previously known "xenobiotic receptor," could mediate a Srebp-independent lipogenic pathway by activating the free fatty acid uptake transporter Cd36. The goal of this study is to investigate further the role of Cd36 in hepatic steatosis.

FXR-mediated regulation of eNOS expression in vascular endothelial cells.

Aims: The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is highly expressed in liver, kidney, adrenals, and intestine. FXR was previously proposed to play an important role in the pathogenesis of cardiovascular diseases via regulating the metabolism and transport of cholesterol. We have recently shown that FXR is also expressed in rat pulmonary vascular endothelial cells (EC) and that activation of FXR leads to inhibition of endothelin-1 expression.

FXR-mediated regulation of angiotensin type 2 receptor expression in vascular smooth muscle cells.

Aims: The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily and plays an important role in the pathogenesis of cardiovascular diseases via regulating the metabolism and transport of cholesterol. We and others have recently shown that FXR is also expressed in the vasculature, including endothelial cells and smooth muscle cells (SMC). However, the biological significance of FXR activation in SMC is still poorly understood.

Downregulation of endothelin-1 by farnesoid X receptor in vascular endothelial cells.

The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is highly expressed in liver, kidney, adrenals, and intestine. FXR may play an important role in the pathogenesis of cardiovascular diseases via regulating the metabolism and transport of cholesterol. In this study, we report that FXR is also expressed in rat pulmonary artery endothelial cells (EC), a "nonclassical" bile acid target tissue.