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The role of endoplasmic reticulum (ER) stress is a rapidly emerging field of interest in the pathogenesis of metabolic diseases. Recent studies have shown that chronic activation of ER stress is closely linked to dysregulation of lipid metabolism in several metabolically important cells including hepatocytes, macrophages, β-cells, and adipocytes. Adipocytes are one of the major cell types involved in the pathogenesis of the metabolic syndrome. Recent advances in dissecting the cellular and molecular mechanisms involved in the regulation of adipogenesis and lipid metabolism indicate that activation of ER stress plays a central role in regulating adipocyte function. In this paper, we discuss the current understanding of the potential role of ER stress in lipid metabolism in adipocytes. In addition, we touch upon the interaction of ER stress and autophagy as well as inflammation. Inhibition of ER stress has the potential of decreasing the pathology in adipose tissue that is seen with energy overbalance. [ABSTRACT FROM AUTHOR]

Background: HIV protease inhibitor (PI)-induced inflammatory response in macrophages is a major risk factor for cardiovascular diseases. We have previously reported that berberine (BBR), a traditional herbal medicine, prevents HIV PIinduced inflammatory response through inhibiting endoplasmic reticulum (ER) stress in macrophages. We also found that HIV PIs significantly increased the intracellular concentrations of BBR in macrophages. However, the underlying mechanisms of HIV PI-induced BBR accumulation are unknown. This study examined the role of P-glycoprotein (P-gp) in HIV PI-mediated accumulation of BBR in macrophages. Methodology and Principal Findings: Cultured mouse RAW264.7 macrophages, human THP-1-derived macrophages, Wild type MDCK (MDCK/WT) and human P-gp transfected (MDCK/P-gp) cells were used in this study. The intracellular concentration of BBR was determined by HPLC. The activity of P-gp was assessed by measuring digoxin and rhodamine 123 (Rh123) efflux. The interaction between P-gp and BBR or HIV PIs was predicated by Glide docking using Schrodinger program. The results indicate that P-gp contributed to the efflux of BBR in macrophages. HIV PIs significantly increased BBR concentrations in macrophages; however, BBR did not alter cellular HIV PI concentrations. Although HIV PIs did not affect Pgp expression, P-gp transport activities were significantly inhibited in HIV PI-treated macrophages. Furthermore, the molecular docking study suggests that both HIV PIs and BBR fit the binding pocket of P-gp, and HIV PIs may compete with BBR to bind P-gp. Conclusion and Significance: HIV PIs increase the concentration of BBR by modulating the transport activity of P-gp in macrophages. Understanding the cellular mechanisms of potential drug-drug interactions is critical prior to applying successful combinational therapy in the clinic. [ABSTRACT FROM AUTHOR]

CeP 2O 7, a close structural relative of ZrP 2O 7, and many other M IVX 2O 7(X – P, V, As) phases, forms on heating Ce(HPO 4) 2· xH 2O between ∼300 and 600 °C and decomposes by oxygen loss at higher temperatures. In-situ X-ray diffraction measurements showed, for some precursor batches, the formation of CeP 2O 7in two distinct stages. At room temperature, CeP 2O 7is pseudocubic, but probably triclinic, displaying positive thermal expansion below ∼115 °C. Above this temperature, there is a transition to cubic symmetry ( Pa3̅) with the linear coefficient of thermal expansion going to zero at ∼450 °C and becoming negative at higher temperatures. CeP 2O 7probably undergoes two phase transitions on compression below ∼10.5 GPa. The phase existing between 0.65 and ∼5 GPa is soft with an average bulk modulus of ∼18 GPa. [ABSTRACT FROM AUTHOR]