Angiotensin II Type 1 Receptor Antagonist Attenuates Lacrimal Gland,Lung, and Liver Fibrosis in a Murine Model of Chronic Graft-Versus-Host Disease

Chronic graft-versus-host disease (cGVHD), a serious complication following allogeneic HSCT (hematopoietic stem cell transplantation), is characterized by systemic fibrosis. The tissue renin-angiotensin system (RAS) is involved in the fibrotic pathogenesis, and an angiotensin II type 1 receptor (AT1R) antagonist can attenuate fibrosis. Tissue RAS is present in the lacrimal gland, lung, and liver, and is known to be involved in the fibrotic pathogenesis of the lung and liver. This study aimed to determine whether RAS is involved in fibrotic pathogenesis in the lacrimal gland and to assess the effect of an AT1R antagonist on preventing lacrimal gland, lung, and liver fibrosis in cGVHD model mice. We used the B10.D2→BALB/c (H-2^d) MHC-compatible, multiple minor histocompatibility antigen-mismatched model, which reflects clinical and pathological symptoms of human cGVHD. First, we examined the localization and expression of RAS components in the lacrimal glands using immunohistochemistry and quantitative real-time polymerase chain reaction (PCR). Next, we administered an AT1R antagonist (valsartan; 10 mg/kg) or angiotensin II type 2 receptor (AT2R) antagonist (PD123319; 10 mg/kg) intraperitoneally into cGVHD model mice and assessed the fibrotic change in the lacrimal gland, lung, and liver. We demonstrated that fibroblasts expressed angiotensin II, AT1R, and AT2R, and that the mRNA expression of angiotensinogen was greater in the lacrimal glands of cGVHD model mice than in controls generated by syngeneic-HSCT. The inhibition experiment revealed that fibrosis of the lacrimal gland, lung, and liver was suppressed in mice treated with the AT1R antagonist, but not the AT2R antagonist. We conclude that RAS is involved in fibrotic pathogenesis in the lacrimal gland and that AT1R antagonist has a therapeutic effect on lacrimal gland, lung, and liver fibrosis in cGVHD model mice. Our findings point to AT1R antagonist as a possible target for therapeutic intervention in cGVHD.     

Synthesis of Brassinolide Analogs with a Modified Ring B and Their Plant Growth-promoting Activity

7-Aza, 7-thia and 6-deoxo analogs of (22S,23S)- and (22R,23R)-homobrassinolide were synthesized. They were found to possess weak bioactivity in a lamina-inclination test.     

Lewis X-Carrying Neoglycolipids Evoke Selective Apoptosis in Neural Stem Cells

Neurochemical Research - N-glycans carrying the Lewis X trisaccharide [Galβ1-4 (Fucα1-3) GlcNAc] are expressed by neural stem cells (NSCs) exclusively before differentiation, and they...     

Antioxidative activity of hydroxylamines. ESR spectra of radicals derived from hydroxylamines

The antioxidative activity of hydroxylamines was evaluated for the oxidation of tetralin at 61°C and linoleic acid micelles in an aqueous dispersion at 37°C, induced by an azo initiator. The antioxidative efficacy of the hydroxylamines for the oxidation of tetralin was smaller than that of α-tocopherol. However, the hydroxylamines showed more potent antioxidative activity than that of the α-tocopherol against the oxidation of linoleic acid micelles. On the basis of the results of an ESR study and the oxidation product obtained, it is suggested that active position in hydroxylamines depend not only on hydroxyl hydrogen-atom, but also on the allylic hydrogen atom.     

Discovery of a novel olefin derivative as a highly potent and selective acetyl-CoA carboxylase 2 inhibitor with in vivo efficacy

Novel acetyl-CoA carboxylase 2 (ACC2) selective inhibitors were identified by the conversion of the alkyne unit of A-908292 to the olefin linker. Modification of the center and left part of the lead compound 1b improved the ACC2 inhibitory activity and CYP450 inhibition profile, and afforded a highly selective ACC2 inhibitor 2e which showed in vivo efficacy in C57BL/6 mice.     

A survey on social jetlag in Japan: a nationwide,cross-sectional internet survey

Sleep and Biological Rhythms - Misalignment between an individual’s circadian phase and his/her environment due to social imposition is called social jetlag (SJL). SJL has emerged as a public...     

Coelastrella astaxanthina sp. nov. (Sphaeropleales,Chlorophyceae), a novel microalga isolated from an asphalt surface in midsummer in Japan

We taxonomically examined an algal strain (Ki‐4) isolated from a dry asphalt surface in mid‐summer of 2003. The vegetative cells were solitary, covered by a cell wall ornamented with meridional ribs, and contained hollow spherical chloroplasts and a pyrenoid. The cells exhibited a high tolerance to unfavorable photo‐oxidative stress conditions, and in culture developed a reddish coloration due to the accumulation of a water‐soluble astaxanthin‐binding protein, which was identified as a novel protein in organisms. 18S rDNA and ITS2 sequence analyses revealed that Ki‐4 belongs to Coelastrella sensu lato (Scenedesmaceae), but was taxonomically distinct from other members of the genus. On the basis of its phylogenetic position and morphological features, including the structures of cell wall ribs, we identify Ki‐4 as a new algal species in the genus Coelastrella, for which we propose the name Coelastrella astaxanthina sp. nov.     

Seasonal prevalence of arthropods after line thinning of overstocked Japanese cedar (<Emphasis Type="Italic">Cryptomeria japonica</Emphasis> D. Don) plantations in central Japan

We investigated the seasonal changes in the abundance of coleopteran and hymenopteran functional groups to evaluate the ecological suitability of line thinning in overstocked Japanese cedar plantations in central Japan. In line thinning, 3- to 5-m-wide sections of the stand are harvested parallel to the mountain slope and perpendicular to the forest roads. The thinning intensity varies from 25 to 35% of the total number of trees. We compared the seasonal abundance between the thinned stand and the unthinned (control) stand in two plantation forests: a low-elevation Sugi site (4 years since thinning) and a high-elevation Kuchiotani site (6 years since thinning). Most coleopteran and hymenopteran functional groups were consistently more abundant in the thinned stand than in the unthinned stand. The differences in arthropod abundance between the thinned and unthinned stands were mainly caused by marked differences in the abundance of seasonally strongly changing functional groups during their peak seasons. The predators and parasitoids of insects as well as the plant and pollen feeders (plant-dependent functional groups) responded to seasonal changes in the vegetation (food and microhabitats) and microclimate. The ants were less affected by line thinning. Our results indicate that line thinning is an ecologically suitable silvicultural treatment for the improvement of biodiversity conditions in the overstocked plantation forests.     

Effect of Richinus communis lectins on the membrane fluidity of human peripheral lymphocytes

The mobility of Ricinus communis lectins bound to lymphocyte cell surface was determined by fluorescence polarization of fluorescein-labeled lectins. R. communis hemagglutinin and R. communis toxin have high mobility. Furthermore, the change of membrane fluidity upon binding of the lectins to lymphocytes was measured by fluorescence polarization of fluorescent hydrocarbon embedded in the membrane. The hemagglutinin, the toxin and its binding subunit apparently increased the membrane fluidity. The hemagglutinin was also found to have mitogenic activity against human peripheral lymphocytes.