Swelling Poly(ionic liquid)s: Synthesis and Application as Quasi-Homogeneous Catalysts in the Reaction of Ethylene Carbonate with Aniline

Homogeneous catalysts generally show higher catalytic activities, while heterogeneous catalysts are more easily separated from products. To combine the advantages of heterogeneous and homogeneous catalysts has been of great interest for many years. Here, we report a kind of facilely prepared cross-linked poly­(ionic liquid)­s (PILs) with swelling property to increase catalytic activities of heterogeneous catalysts. The swelling ability of PILs was greatly affected by cross-linking density and chain length of substituents on imidazolium, and the unique swelling property prompted the nonporous PILs to contact with substrates sufficiently, enhancing their catalytic activities similar to homogeneous ionic liquid monomers

Association between social support and the general facet on QOL and health.

<p>Association between social support and the general facet on QOL and health.</p

Associations between social support and four domains of HRQOL.

<p>Associations between social support and four domains of HRQOL.</p

AMPK inhibition in metformin’s effects on NFκB, MCP-1, IL-8 and ICAM-1 in hRVECs.

<p>HRVECs were pretreated with metformin, then exposed to TNFα as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193031#pone.0193031.g003" target="_blank">Fig 3</a>. A selective AMPK inhibitor, compound C, was co-administrated to evaluate the role of AMPK signaling in metformin’s influence on hRVECs. <b>(A)</b> Representative images and densitometric analysis of <a target="_blank">p</a>AMPKα immunoblot in hRVECs. TNFα markedly reduced the level of pAMPKα, which was impeded by pretreatment of metformin dose-dependently. <b>(B)</b> Western blot of NFkB p65 and <b>(C)</b> ELISA of IL-8 revealed no obvious changes were caused by addition of compound C in metformin regiment in the presence of TNFα. <b>(D)</b> Western blot of ICAM-1 and <b>(E)</b> ELISA of MCP-1 showed that compound C significantly blocked the inhibition of ICAM-1 and MCP-1 by metformin. Data were normalized to control (without metformin and TNFα) and presented as mean ± SEM (n = 3). ^# <i>p</i> < 0.05 versus control. * <i>p</i> < 0.05 versus TNFα-only group.</p

Effects of metformin on IRNV in <i>vldlr</i>^<i>-/-</i> mice.

<p><i>Vldlr</i>^<i>-/-</i> mice were treated with metformin (200 mg/kg/day) or vehicle solution (control) by daily gavage from P10 to P21. Total number of IRNV sprouts was quantified at P21 in a whole mount retina after isolectin-FITC staining. <b>(A-D)</b> Representative images of isolectin stained retinal whole mounts from control (A, C) and metformin treated (B, D) P21 <i>vldlr</i>^<i>-/-</i> mice. <b>(E)</b> Quantitative measurement showed an over 50% reduction of the number of IRNV sprouts per retina in metformin treated group (n = 25) versus control group (n = 24) (<i>p</i> = 0.0118).</p

Metformin suppresses retinal angiogenesis and inflammation <i>in vitro</i> and <i>in vivo</i>

<div><p>The oral anti-diabetic drug metformin has been found to reduce cardiovascular complications independent of glycemic control in diabetic patients. However, its role in diabetic retinal microvascular complications is not clear. This study is to investigate the effects of metformin on retinal vascular endothelium and its possible mechanisms, regarding two major pathogenic features of diabetic retinopathy: angiogenesis and inflammation. In human retinal vascular endothelial cell culture, metformin inhibited various steps of angiogenesis including endothelial cell proliferation, migration, and tube formation in a dose-dependent manner. Its anti-angiogenic activity was confirmed <i>in vivo</i> that metformin significantly reduced spontaneous intraretinal neovascularization in a very-low-density lipoprotein receptor knockout mutant mouse (<i>p</i><0.05). Several inflammatory molecules upregulated by tumor necrosis factor-α in human retinal vascular endothelial cells were markedly reduced by metformin, including nuclear factor kappa B p65 (NFκB p65), intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8). Further, metformin significantly decreased retinal leukocyte adhesion (<i>p</i><0.05) in streptozotocin-induced diabetic mice. Activation of AMP-activated protein kinase was found to play a partial role in the suppression of ICAM-1 and MCP-1 by metformin, but not in those of NFκB p65 and IL-8. Our findings support the notion that metformin has considerable anti-angiogenic and anti-inflammatory effects on retinal vasculature. Metformin could be potentially used for the purpose of treating diabetic retinopathy in addition to blood glucose control in diabetic patients.</p></div

Ceramide as a Mediator of Non-Alcoholic Fatty Liver Disease and Associated Atherosclerosis

<div><p>Cardiovascular disease (CVD) is a serious comorbidity in nonalcoholic fatty liver disease (NAFLD). Since plasma ceramides are increased in NAFLD and sphingomyelin, a ceramide metabolite, is an independent risk factor for CVD, the role of ceramides in dyslipidemia was assessed using LDLR-/- mice, a diet-induced model of NAFLD and atherosclerosis. Mice were fed a standard or Western diet (WD), with or without myriocin, an inhibitor of ceramide synthesis. Hepatic and plasma ceramides were profiled and lipid and lipoprotein kinetics were quantified. Hepatic and intestinal expression of genes and proteins involved in insulin, lipid and lipoprotein metabolism were also determined. WD caused hepatic oxidative stress, inflammation, apoptosis, increased hepatic long-chain ceramides associated with apoptosis (C16 and C18) and decreased very-long-chain ceramide C24 involved in insulin signaling. The plasma ratio of ApoB/ApoA1 (proteins of VLDL/LDL and HDL) was increased 2-fold due to increased ApoB production. Myriocin reduced hepatic and plasma ceramides and sphingomyelin, and decreased atherosclerosis, hepatic steatosis, fibrosis, and apoptosis without any effect on oxidative stress. These changes were associated with decreased lipogenesis, ApoB production and increased HDL turnover. Thus, modulation of ceramide synthesis may lead to the development of novel strategies for the treatment of both NAFLD and its associated atherosclerosis.</p></div

Effects of metformin on angiogenic activities and apoptosis of hRVECs.

<p><b>(A)</b> Proliferation assay showed that metformin treatment at 5–50mM for 24 hours reduced hRVEC proliferation dose-dependently. <b>(B)</b> <i>In vitro</i> TUNEL assay revealed that exposure to 50 mM or lower metformin for 24 hours did not induce hRVECs apoptosis compared with negative control. Apoptosis of hRVECs was only seen when metformin dose reached 100 mM or higher. <b>(C)</b> Representative images and <b>(D)</b> quantitative analysis of scratch assay indicated a 12 hour treatment with metformin at 10–50 mM reduced hRVECs migration in a dose-dependent pattern. <b>(E)</b> Representative images and <b>(F)</b> quantitative analysis of hRVEC tube formation. After exposure to metformin at 0–50 mM for 6 hours, total length of capillary-like network formed by hRVECs decreased significantly and dose-dependently. Data were normalized to non-metformin treated control (in A, D, F) or DNase I treated positive control (in B) and presented as mean ± SEM (n = 3). * <i>p</i> < 0.05 versus non-metformin treated control.</p

Effects of metformin pretreatment on NFκB, MCP-1, IL-8 and ICAM-1 in hRVECs with TNFα challenge.

<p>Cells were exposed to 2.5 ng/mL recombinant TNFα for 12 hours with or without 12-hour pretreatment of 5–40 mM metformin. The expression of NFκB p65 and ICAM-1 in hRVECs was measured by western blot. The concentration of MCP-1 and IL-8 in hRVEC culture media was determined using ELISA kits. (A) Representative blots and densitometry analysis revealed that TNFα upregulated expression of NFkB p65 in hRVECs, which was dramatically inhibited by metformin at 5–40 mM. (B) ELISA assay revealed that 5 mM metformin significantly blocked TNFα-induced secretion of MCP-1 and IL-8. (C) Representative blots and band intensity measurement of ICAM-1 immunoblot showed that metformin at 5 mM markedly prevented TNFα-induced upregulation of ICAM-1 in hRVECs. Data were normalized to control (without metformin or TNFα) and presented as mean ± SEM (n = 3). * <i>p</i> < 0.05 versus TNFα only group.</p

Effects of metformin on retinal leukostasis in STZ-induced diabetic mice.

<p>STZ-induced diabetic mice were treated with metformin (200 mg/kg/day) or balanced salt solution by daily gavage after 5 days of STZ injection for 10 weeks. Age-matched nondiabetic mice were used as wild type control. Retinal leukostasis was examined by perfusion labeling with FITC-coupled Con A. <b>(A-C)</b> Representative images of retinal flat mounts from wild type mice (A) and STZ-induced diabetic mice with (C) or without metformin treatment (B). Arrows indicated adherent leukocytes in retinal vasculature. <b>(D)</b> Quantification analysis showed a significant higher number of leukocytes per retina in STZ-induced diabetic mice versus wild type control, which was significantly reduced by metformin treatment. WT, wild type mice. STZ, STZ-induced diabetic mice treated with balanced salt solution. STZ+Met, STZ-induced diabetic mice treated with metformin. ^# <i>p</i> < 0.05 versus wild type mice; * <i>p</i> < 0.05 versus STZ-induced diabetic mice treated with vehicle solution.</p