Deformation of Lipid Membranes Containing Photoresponsive Molecules in Response to Ultraviolet Light

Recently, membrane deformation using photoresponsive molecules has been extensively studied toward controlling their shapes because light can supply energy without contacting the vesicles. In this study, photoresponsive <i>pseudogem</i>-bis­(diphenylimidazole) [2.2]­paracyclophane (<i>pseudogem</i>-bisDPI­[2.2]­PC) molecules were doped into dioleoylphosphatidylcholine (DOPC) membranes, and the deformation of the DOPC/<i>pseudogem</i>-bisDPI­[2.2]­PC vesicles was observed under ultraviolet (UV)-light irradiation. It was also found that the volume-to-surface area ratio of spherical vesicles was changed by UV irradiation. Further, we performed high performance liquid chromatography (HPLC) analysis of membrane components in order to clarify the absence of irreversible chemical reactions and UV-irradiation experiments under an osmotic pressure in order to investigate the volume change of the vesicles. Then, we calculated the time-correlation function of membrane fluctuation. Change in the relaxation time of the time-correlation function indicated that the photoisomerization of <i>pseudogem</i>-bisDPI­[2.2]­PC might decrease the membrane fluidity. We consider that decreasing fluidity is induced by physical entanglement between photochromic compounds and lipids. This technique of membrane deformation may be expected to be applied to various situations such as drug delivery systems (DDS)

Effect of Adiponectin on Kidney Crystal Formation in Metabolic Syndrome Model Mice via Inhibition of Inflammation and Apoptosis

<div><p>The aims of the present study were to elucidate a possible mechanism of kidney crystal formation by using a metabolic syndrome (MetS) mouse model and to assess the effectiveness of adiponectin treatment for the prevention of kidney crystals. Further, we performed genome-wide expression analyses for investigating novel genetic environmental changes. Wild-type (+/+) mice showed no kidney crystal formation, whereas ob/ob mice showed crystal depositions in their renal tubules. However, this deposition was remarkably reduced by adiponectin. Expression analysis of genes associated with MetS-related kidney crystal formation identified 259 genes that were >2.0-fold up-regulated and 243 genes that were <0.5-fold down-regulated. Gene Ontology (GO) analyses revealed that the up-regulated genes belonged to the categories of immunoreaction, inflammation, and adhesion molecules and that the down-regulated genes belonged to the categories of oxidative stress and lipid metabolism. Expression analysis of adiponectin-induced genes related to crystal prevention revealed that the numbers of up- and down-regulated genes were 154 and 190, respectively. GO analyses indicated that the up-regulated genes belonged to the categories of cellular and mitochondrial repair, whereas the down-regulated genes belonged to the categories of immune and inflammatory reactions and apoptosis. The results of this study provide compelling evidence that the mechanism of kidney crystal formation in the MetS environment involves the progression of an inflammation and immunoresponse, including oxidative stress and adhesion reactions in renal tissues. This is the first report to prove the preventive effect of adiponectin treatment for kidney crystal formation by renoprotective activities and inhibition of inflammation and apoptosis.</p></div

Confirmation of selected genes detected by microarray analysis.

<p>A–F. Among the selected genes with significant expression changes in the microarray analysis, the expression of several characteristic genes belonging to 6 categories based on GO analysis was evaluated by immunohistochemical staining. Magnification is ×20 (in box: ×400). 6 categories are as follows. A. Inflammation and immune-related gene group: LYZ1, Lysozyme 1.CD44, CD44 antigen; MHC-class 2, major histocompatibility complex-class2. B. Apoptosis-related gene group: STAT3, signal transducer and activator of transcription 3; AURKA, aurora kinase A, Thymidine kinase 1, C. Cell repair and proliferation-related gene group: MCM5, minichromosome maintenance deficient 5. D. Adhesion and fibrosis-related gene group: Fn, Fibronectin. E. Oxidative stress-related gene group: 8OHdG, 8-Hydroxydeoxyguanosine. F: transporter-related gene group; SLC12A1, solute carrier family 12, member 1.</p

Confirmation that selected genes detected by microarray analysis showed differential expression between different treatment groups.

<p>The expression of several characteristic genes belonging to 5 categories based on GO analysis was evaluated by quantitative PCR. Expression levels are expressed relative to <i>Actb</i>. Data are indicated as the mean ± SE. *, p<0.05 between the groups at the same time point. †, p<0.01 compared with the same group at day 0. 5 categories are as follows. A. Inflammation and immune-related gene group: <i>Lcn2</i>, lipocalin2; <i>Cd44</i>, CD44 antigen; <i>Lyz1</i>, lysozyme1. B. Apoptosis-related gene group: <i>Stat3</i>, signal transducer and activator of transcription 3; <i>Aurka</i>, aurora kinase A. C. Cell repair and proliferation-related gene group: <i>Mcm5</i>, minichromosome maintenance deficient 5. D. Adhesion and fibrosis-related gene group: <i>Vcam1</i>, vascular cell adhesion molecule 1; <i>Col3a1</i>, collagen, type III, alpha 1. E. Transporter-related gene group: <i>Slc12a1</i>, solute carrier family 12, member 1; <i>Slc7a13</i>, solute carrier family 7, member 13.</p

Expression analyses of <i>Spp1</i>, <i>Sod2</i>, <i>Ccl2</i>, and <i>Adipoq</i>.

<p>A. The results of quantitative PCR for the expression of <i>Spp1</i>, <i>Sod2</i>, <i>Ccl2</i>, and <i>Adipoq</i>. Expression levels are expressed relative to <i>Actb</i> (<i>actin-beta</i>) transcript levels. <i>Spp1</i>, secreted phosphoprotein 1; <i>Ccl2</i>, C-c chemokine ligands 2; <i>Sod2</i>, superoxide dismutase 2; <i>Adipoq</i>, adiponectin. Data are indicated as the mean ± SE. *, p<0.05 between groups at the same time point. †, p<0.01 compared with the same group at day 0. B. Immunohistochemical staining for OPN, MCP-1, SOD, and APN expression. OPN, osteopontin; MCP-1, monocyte chemotactic protein-1; SOD, superoxide dismutase; APN, adiponectin. Magnification is ×20 (in box: ×400). C. The quantification of immunohistochemical staining. Data are indicated as the mean ± SD. *, p<0.05 between groups at the same time point. †, p<0.05 compared with the same group at day 0.</p

TUNEL staining and the number of TUNEL-positive cells.

<p>Data are indicated as the mean ± SD. *, p<0.05 between groups at the same time. **, p<0.01 between groups at the same time point. †, p<0.01 compared with the same group at day 6.</p

Detection and quantification of calcium oxalate kidney crystal formation.

<p>A. Kidney sections of wild type (+/+), obesity (ob/ob), and adiponectin-treated ob/ob (ob/ob+APN) mice at day 6. The upper images show calcium oxalate crystal deposits in Pizzolato-stained sections. The lower images show non-stained sections observed by polarized light optical microphotography (PLOM). Magnification is ×20 (in box: ×400). B. Quantification of kidney crystals in +/+, ob/ob, and ob/ob+APN mice. Data are indicated as the mean ± SD. a; p = 0.0004, b; p = 0.005.</p

The scheme of the microarray analysis design.

<p>A. Experimental design and gene expression changes between groups. <i>Δ</i> refers to a gene group with >2.0- or <0.5-fold expression change between 2 experimental groups. <i>ΔA</i> means gene expression involving GOx administration. <i>ΔB</i> means gene expression involving obesity. <i>ΔC</i> means gene expression involving GOx administration and kidney stone formation. <i>ΔD</i> means gene expression involving obesity and kidney stone formation. <i>ΔE</i> means gene expression involving obesity, GOx administration, and kidney stone formation. <i>ΔF</i> means gene expression involving APN administration and kidney stone prevention. +GOx, glyoxylate administration; +APN, adiponectin treatment. B. The selection scheme for kidney stone formation-related gene groups (Venn diagram). The gray-stained area is represented by (<i>ΔC</i>∩<i>ΔD</i>∩<i>ΔE</i>)\(<i>ΔA</i>∪<i>ΔB</i>) and is the kidney stone formation-specific gene group under a MetS environment.</p

Confirmation of selected genes detected by microarray analysis.

<p>Western blot analysis for OPN, MCP-1, SOD, APN, LYZ1, AURKA, TK1, MCM5, NGAL, CD44, STAT3, SLC12A1, SLC7A13, VCAM1, COL3A1 and FN protein expression. Each molecular weight demonstrated as the bands were as follows. OPN, 75 and 55 kDa; MCP-1,17 kDa; SOD, 37 kDa; APN, 64 kDa; LYZ1, 17 kDa; AURKA, 40 kDa; TK1, 25 kDa; MCM5, 90 kDa; NGAL, 25 kDa; CD44, 80–95 kDa; STAT3, 92 kDa; SLC12A1, 47 kDa; SLC7A13, 52 kDa; VCAM1, 100 kDa; COL3A1, 138 kDa; FN, 212 kDa and β-actin, 37 kDa.</p

Chronic Kidney Disease Is Positively and Diabetes Mellitus Is Negatively Associated with Abdominal Aortic Aneurysm

<div><p>Background and Aims</p><p>Chronic kidney disease (CKD) and diabetes mellitus (DM) are considered as risk factors for cardiovascular diseases. The purpose of this study was to clarify the relationship of CKD and DM with the presence of abdominal aortic aneurysm (AAA).</p><p>Methods</p><p>We enrolled 261 patients with AAA (AAA+) and age-and-sex matched 261 patients without AAA (AAA-) at two hospitals between 2008 and 2014, and examined the association between the risk factors and the presence of AAA. Furthermore, in order to investigate the prevalence of AAA in each group, we enrolled 1126 patients with CKD and 400 patients with DM.</p><p>Results</p><p>The presence of CKD in patients with AAA+ was significantly higher than that in patients with AAA- (AAA+; 65%, AAA-; 52%, <i>P</i> = 0.004). The presence of DM in patients with AAA+ was significantly lower than that in patients with AAA- (AAA+; 17%, AAA-; 35%, <i>P</i> < 0.001). A multivariate logistic regression analysis demonstrated that hypertension, ischemic heart disease and CKD were independent determinants, whereas, DM was a negatively independent determinant, for the presence of AAA. The prevalence of AAA in patients with CKD 65 years old and above was 5.1%, whereas, that in patients with DM 65 years old and above was only 0.6%.</p><p>Conclusion</p><p>CKD is a positively associated with the presence of AAA. In contrast, DM is a negatively associated with the presence of AAA in Japanese population.</p></div