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We report a swinging motion of photochromic thin broad sword shaped crystals upon continuous irradiation with UV light. By contrast in thick crystals, photosalient phenomena were observed. The bending and swinging mechanisms are in fact due to molecular size changes as well as phase transitions. The first slight bending away from the light source is due to photocyclization-induced surface expansion, and the second dramatic bending toward UV incidence is due to single-crystal-to-single-crystal (SCSC) phase transition from the original phase I to phase IIUV. Upon visible light irradiation, the crystal returned to phase I. A similar SCSC phase transition with a similar volume decrease occurred by lowering the temperature (phase IIItemp). For both photoinduced and thermal SCSC phase transitions, the symmetry of the unit cell is lowered; in phase IIUV the twisting angle of disordered phenyl groups is different between two adjacent molecules, while in phase IIItemp, the population of the phenyl rotamer is different between adjacent molecules. In the case of phase IIUV, we found thickness dependent photosalient phenomena. The thin broad sword shaped crystals with a 3 μm thickness showed no photosalient phenomena, whereas photoinduced SCSC phase transition occurred. In contrast, large crystals of several tens of μm thickness showed photosalient phenomena on the irradiated surface where SCSC phase transition occurred. The results indicated that the accumulated strain, between isomerized and non-isomerized layers, gave rise to the photosalient phenomenon., We report a swinging motion of photochromic thin broad sword shaped crystals upon continuous irradiation with UV light.

Background & Aims Mesalamine is a first-line drug for treatment of inflammatory bowel diseases (IBD). However, its mechanisms are not fully understood. CD4+ Foxp3+ regulatory T cells (Tregs) play a potential role in suppressing IBD. This study determined whether the anti-inflammatory activity of mesalamine is related to Treg induction in the colon. Methods We examined the frequencies of Tregs in the colons of wild-type mice, mice deficient for aryl hydrocarbon receptor (AhR-/- mice), and bone marrow–chimeric mice lacking AhR in hematopoietic cells (BM-AhR-/- mice), following oral treatment with mesalamine. We also examined the effects of mesalamine on transforming growth factor (TGF)-β expression in the colon. Results Treatment of wild-type mice with mesalamine increased the accumulation of Tregs in the colon and up-regulated the AhR target gene Cyp1A1, but this effect was not observed in AhR-/- or BM-AhR-/- mice. In addition, mesalamine promoted in vitro differentiation of naive T cells to Tregs, concomitant with AhR activation. Mice treated with mesalamine exhibited increased levels of the active form of TGF-β in the colon in an AhR-dependent manner and blockade of TGF-β signaling suppressed induction of Tregs by mesalamine in the colon. Furthermore, mice pretreated with mesalamine acquired resistance to dextran sodium sulfate–induced colitis. Conclusions We propose a novel anti-inflammatory mechanism of mesalamine for colitis: induction of Tregs in the colon via the AhR pathway, followed by TGF-β activation., Graphical abstract

The structural evolution with the self-assembly and self-alignment progress of the typical Lyotropic Chromonic Liquid Crystals (LCLCs) molecules, Sunset Yellow FCF (SSY), was studied by time-resolved grazing-incidence wide-angle X-ray scattering (GI-WAXS). It was revealed that the SSY molecules oriented by the initial shear flow gradually assembled and was oriented by solvent evaporation. Then, the drastic progress in the assembly and orientation occurred accompanying the electrostatic interaction between the assembled aggregates.

Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that plays a crucial role in protection of cells from electrophile-induced toxicity through up-regulating phase II detoxifying enzymes and phase III transporters. We previously reported that oxidative stress induces up-regulation of interleukin-11 (IL-11), a member of the IL-6 family that ameliorates acetaminophen-induced liver toxicity. However, a role for IL-11 in protection of cells from electrophile-induced toxicity remains unclear. Here we show that an environmental electrophile, 1,2-naphthoquinone (1,2-NQ), but not 15d-prostaglandin J2 (PGJ2) or tert-butylhydroxyquinone (tBHQ), induced IL-11 production. Consistent with a crucial role for prolonged ERK activation in H2O2-induced IL-11 production, 1,2-NQ, but not 15d-PGJ2 or tBHQ, elicited prolonged ERK activation. Conversely, inhibition of the ERK pathway by a MEK inhibitor completely blocked 1,2-NQ-induced IL-11 production at both protein and mRNA levels, further substantiating an intimate cross-talk between ERK activation and 1,2-NQ-induced IL-11 production. Promoter analysis of the Il11 gene revealed that two AP-1 sites were essential for 1,2-NQ-induced promoter activities. Among various members of the AP-1 family, Fra-1 was up-regulated by 1,2-NQ, and its up-regulation was blocked by a MEK inhibitor. Although NRF2 was not required for H2O2-induced IL11 up-regulation, NRF2 was essential for 1,2-NQ-induced IL11 up-regulation by increasing Fra-1 proteins possibly through promoting mRNA translation of FOSL1. Finally, intraperitoneal administration of 1,2-NQ induced body weight loss in wild-type mice, which was further exacerbated in Il11ra1−/− mice compared with Il11ra1+/− mice. Together, both Fra-1 and NRF2 play crucial roles in IL-11 production that protects cells from 1,2-NQ intestinal toxicity.

By alternate irradiation with UV and visible light, reversible topographical changes were observed on the microcrystalline surfaces of diarylethene derivatives above the glass transition temperatures (Tg) of their open-ring isomers. For the photogenerated closed-ring isomers, the crystal growth proceeded at the surface softened by molecular movement. This is the self-aggregation of the closed-ring isomers. The photogenerated surface topographies appear depending on the crystal habits of the closed-ring isomers. Reflecting the properties (crystal habits) of diarylethene derivatives, we obtained cubic, needle, and plate-shaped crystals of the closed-ring isomers on the microcrystalline surfaces of the open-ring isomers by irradiation with UV light. Even a derivative having one isopropyl group at a reactive carbon atom, whose closed-ring isomer is thermally unstable, showed photoinduced topographical changes, because the Tg of the open-ring isomer is around ambient temperature.

We identified the mechanism of the formation of needle-shaped microcrystals on which the contact angle of a water droplet exceeds 170° [Nishikawa, N. et al. Langmuir, 2012, 28, 17817-17824]. The standing needle-shaped crystal of the closed-ring isomer of a diarylethene 3c grew at a much lower temperature than the eutectic temperature by irradiation of UV light on the thin films of the open-ring isomer 3o, due to the epitaxial growth of the 013 plane of 3c over the 110 plane of the crystal lattice of 3o in the subphase. Therefore, the new crystal-growth mechanism triggered by the photoisomerization does not require special inorganic single-crystal substrates and may be called self-epitaxial crystal growth. The needle-shaped crystals appeared well-ordered and stood inclined at an angle of about 60° to the surface. Consequently, the photo-induced rough surface shows not only the superhydrophobic lotus effect, but also the antireflection moth-eye effect, and these effects were switchable by alternate irradiation with UV and visible light.

When carbohydrate metabolism is impaired, fatty acid metabolism is activated. Excess acetyl-coenzyme A (CoA) is generated from fatty acids by β-oxidation and is used for the formation of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) and subsequently for acetoacetate. High levels of secreted ketone bodies (acetoacetate and 3β-hydroxybutyrate) lower the pH of blood and urine, resulting in ketoacidosis. HMG-CoA lyase in hepatic cells is a rate-limiting enzyme catalyzing the cleavage of HMG-CoA to acetoacetate, and thus inhibition of this enzyme results in reduced acetoacetate production, in other words, impaired ketoacidosis. Inhibition of HMG-CoA lyase activity possibly prevents ketoacidosis and should be the therapeutic target. Polyphenols are common and abundant dietary constituents with beneficial effects on human health. We examined the inhibitory effects of dietary polyphenols on HMG-CoA lyase activity in cellular extracts of human hepatoma HepG2 cells. Of the nine representative dietary polyphenols tested, (-)-epigallocatechin (EGC), (-)-epigallocatechin gallate (EGCG), and gallic acid (GA) effectively inhibited HMG-CoA lyase activity. Lineweaver-Burk analysis revealed that EGC and EGCG are likely to be mixed-type noncompetitive inhibitors. Pyrogallol with the gallyl structure also inhibited HMG-CoA lyase activity, suggesting that the gallyl moiety of polyphenols is important for the inhibition of HMG-CoA lyase activity.

When visible light is irradiated onto the melted microcrystalline-surface of a diarylethene having ionic structures by UV irradiation, it induces crystal-growth of the open-ring isomer of the diarylethene; consequently, the surface covered with lumpy crystals shows superhydrophilicity that can be reversibly controlled by alternating irradiation with UV and visible light.

A superhydrophobic surface on which the contact angle of a water droplet exceeds 170° was reversibly produced by alternate irradiation with UV and visible light. Superhydrophobicity is due to the formation of densely generated submicrometer sized needle-shaped crystals (less than 0.2-0.3 μm diameter and 2.2-2.5 μm long) at 30 °C, which is much lower than the eutectic temperature of either isomers of the diarylethene. Below the eutectic temperature, the generated crystals were much smaller than those generated above the eutectic temperature. These smaller crystals more effectively enhanced the superhydrophobicity.

Diarylethene 1 shows reversible transformation between the open-ring isomer (1o) and the closed-ring isomer (1c) by alternate UV and visible light irradiation, accompanied with reversible melting and crystallization of the microcrystalline film of 1 at 67 °C, which is the eutectic temperature of 1o and 1c. The reversible epitaxial crystal growth of an 1o of a diarylethene derivative was observed on a 110 surface of a strontium titanate (SrTiO3) single crystal by maintaining a constant temperature and monitoring six reversible intensity changes (within 2 h of repeating cycles) of the reflection of 004 of 1o on XRD measurements.

By alternate UV and visible light irradiation, reversible topographical changes were observed on a newly synthesized diarylethene microcrystalline surface between the rough crystalline surface of an open-ring isomer and flat eutectic surfaces. The contact angle changes of a water droplet between 80° and 150° and peak intensities changes of the open-ring isomer in XRD patterns within 2 h of repeating cycle were observed. The results indicated that reversibly photogenerated rod-shaped crystals on the surface were produced based on the lattice of the open-ring isomer crystals in the subphase.

Hypoglycemia is one of the serious adverse effects induced by cibenzoline (CBZ), an antiarrhythmic agent. In order to clarify the pharmacodynamics of CBZ-induced hypoglycemia, CBZ was administered intravenously to conscious rats at a dose of 5, 10 or 20 mg/kg and serum samples were collected periodically to determine the concentrations of CBZ, insulin and glucose. The pharmacokinetics of CBZ showed nonlinear characteristics and could be described by a two-compartment model with Michaelis-Menten elimination kinetics. CBZ induced a rapid increase in the serum concentration of insulin. As the CBZ dose was increased, a greater hypoglycemic effect occurred. The indirect response model was applied to account for the CBZ-induced increase in insulin secretion and the subsequent decrease in serum glucose. A linear relationship was assumed between the serum concentration of CBZ and its stimulating effect on insulin secretion. A nonlinear relationship was assumed between the serum concentration of insulin and its stimulating effect on the elimination of serum glucose. The time courses of serum concentrations of CBZ, insulin and glucose after intravenous injection of CBZ could be described by the pharmacokinetic and pharmacodynamic model developed. This approach will be useful for the identification of variable factors related to CBZ-induced hypoglycemia.

We showed previously that adult small bowel could be transplanted successfully in rats without vascular reconstruction by removing the graft serosa. In this study, we assessed if granulocyte colony-stimulating factor (G-CSF) or basic fibroblast growth factor (bFGF) could improve graft survival in the same rat model.A 10-mm-long adult small bowel graft from an adult 12-week-old Lewis rat was transplanted into a pouch created in the omentum of a 5-week-old Lewis rat (syngeneic bowel transplantation [SBTx], n = 49). Graft serosa was removed just before SBTx in the serosectomy group (n = 29) and left intact in the nonserosectomy group (n = 20). Each group was divided into 3 subgroups (sG): sG-1 had no G-CSF or bFGF; sG-2 had daily subcutaneous injections of G-CSF; and sG-3 had continuous infusion of bFGF around the graft in the omentum. All grafts were harvested 14 days after SBTx and studied histologically. A mucosal surface expansion score (MSES) was used where 0 = no mucosa on the graft, 1 = mucosa on one fourth of the graft, 2 = mucosa on one half of the graft, 3 = mucosa on three fourths of the graft, and 4 = mucosa on the whole graft. The density of CD34-positive capillaries per 1000 nuclei was also measured.Serosectomy group MSES were significantly higher than nonserosectomy group MSES indicating that grafts survived (P.0001). CD34-positive capillaries in serosectomy group subgroups for mucosa were 103.9 +/- 34.2, 130.2 +/- 52.0, and 132.3 +/- 37.7, respectively; for muscle, 74.4 +/- 38.0, 86.2 +/- 32.9, and 82.4 +/- 30.3, respectively; and for omentum, 73.8 +/- 30.1, 151.3 +/- 60.3, and 140.0 +/- 49.0, respectively. Mucosal surface expansion score and overall CD34-positive capillaries for sG-2 and sG-3 were significantly higher than for sG-1 (both, P.05).Our results suggest that G-CSF and bFGF enhance angiogenesis and mucosal surface expansion.

The aim of this study was to assess whether adult small bowel grafts (ASBGs) can survive transplantation without vascular reconstruction if graft serosectomy (SS) is performed.Syngeneic ASBG transplants were performed in 85 Lewis rats. The entire serosa was removed just before transplantation in the SS group (n = 50) and left intact in the nonserosectomy group (n = 35). Transplanted ASBG was harvested 1, 3, 5, 7, 14, 21, or 28 days after transplantation and studied using staining with hematoxylin-eosin, immunohistochemistry for protein gene product 9.5, S-100, CD34 and vascular endothelial growth factor (VEGF), and quantification of VEGF messenger RNA (mRNA). Adult small bowel graft viability was assessed blindly using a mucosal surface expansion score (0, no mucosa; 1, mucosa on one fourth of graft; 2, mucosa on one half of graft; 3, mucosa on three fourths of graft; and 4, circumferential mucosa on graft).No rejection was identified in any ASBG. Average mucosal surface expansion score and VEGF mRNA expression were significantly higher in the SS group (both P.01). Vascular endothelial growth factor protein was detected in enterocytes from day 3 posttransplant in the SS group. Distribution of protein gene product 9.5 and S-100 was normal in SS-group ASBG.Our results suggest that SS allows VEGF mRNA and, subsequently, VEGF protein in ASBG to be induced very soon after transplantation, which may contribute to the survival of ASBG transplanted without vascular reconstruction.

Smad3 deficiency attenuates renal fibrosis, inflammation, and apoptosis after unilateral ureteral obstruction. Background Transforming growth factor-β (TGF-β) has been implicated in the development of renal fibrosis induced by unilateral ureteral obstruction (UUO). However, there is little information on signaling pathways mediating TGF-β activity involved in molecular and cellular events leading to renal fibrosis induced by UUO. In this study, we sought to determine whether Smad3, a major signaling component of TGF-β, mediated renal fibrosis induced by UUO. Methods Renal fibrosis, inflammation, and apoptosis induced by UUO were macroscopically and histologically compared between wild-type mice and Smad3 null mice. Results Gross appearance of the kidney after UUO showed relatively intact kidney in Smad3 null mice [Smad3(-/-) mice] when compared with that of wild-type mice [Smad3(+/+) mice]. Renal interstitial fibrosis based on the interstitial area stained with Aniline-blue or Sirius red solution was significantly attenuated in the obstructed kidney of Smad3(-/-) mice when compared with that of Smad3(+/+) mice. Deposition of type I and type III collagens were also significantly reduced in the obstructed kidney of Smad3(-/-) mice. In addition, the numbers of myofibroblasts, macrophages, and CD4/CD8 T cells infiltrated into the kidney after UUO were significantly attenuated in the obstructed kidney of Smad3(-/-) mice when compared with that of Smad3(+/+) mice. Furthermore, terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) staining after UUO showed significantly reduced number of tubular apoptotic cells in the obstructed kidney of Smad3(-/-) mice when compared with that of Smad3(+/+) mice. Endogenous Smadpathway was activated in the obstructed kidney after UUO in wild-type mice as judged by the increase of phosphorylated Smad2 or phosphorylated Smad2/3-positive cells in renal interstitial area. Conclusion Smad3 deficiency attenuated renal fibrosis, inflammation, and apoptosis after UUO, suggesting that Smad3 was a key molecule mediating TGF-β activity leading to real fibrosis after UUO.

Achiral host molecules, tetrakis(4-ethynylphenyl)ethylene 3 and tetrakis(4-bromoethynylphenyl)ethylene 4, formed chiral host–guest inclusion crystals with achiral guest molecules via weak intermolecular interactions.

This paper reports on the crystal structures of the three silicon phthalocyanines: dichlorosilicon phthalocyanine [SiCl2Pc], dimethoxysilicon phthalocyanine [Si(Ome)2Pc] and bis(tetrahydrofurfuryloxy)silicon phthalocyanine [Si(thff)2Pc]. We found that although Si(Ome)2Pc and Si(thff)2Pc show sensitivity for an electrophotographic photoreceptor, SiCl2Pc doesn't have photosensitivity. It is known that the difference in the photochemical property of phthalocyanines is related to the crystal structures. Although it is difficult for these materials to obtain single crystals with sufficient size for single crystal X-ray analysis, it is very important to determine the crystal structures in order to understand the mechanism concerning the performance of the electrophotographic photoreceptor. In this work we determined the crystal structures from very small (micrometer-sized) single crystals. The compounds crystallized in space group P21/n for SiCl2Pc, Z = 2 with unit-cell parameters a = 10.261(1) A, b = 14.618(2)...

This paper reports on the synthesis and ab-initio X-ray powder structure determination of two polymorphs of [Si(OH)2Pc], where Pc = phtalocyaninato. We found that one of the polymorphs (Phase II) shows high sensitivity for an electrophotographic photoreceptor, but that the other (Phase I) doesn’t have photosensitivity. The difference in the sensitivity depends on only the crystal structures. This material has not been able to be grown to a single crystal with sufficient size for single crystal X-ray analysis, but it is very important to determine the crystal structures of the two polymorphs for understanding the mechanism of the performance of the electrophotographic photoreceptor. In this work we carried out ab-initio X-ray powder structure analysis. The compound crystallizes in space group (Phase I), Z = 1 with unit-cell parameters of a = 12.992(1), b = 7.2830(8), c = 6.861(1) A, α = 104.413(7)°, β = 101.757(8)°, γ = 96.973(6)° and in space group P21/n (Phase II), Z = 2 with unit-cell parameters of a = ...

We previously demonstrated that topical application of fibroblast growth factor (FGF)-2 enhanced periodontal tissue regeneration. Although angiogenesis is a crucial event for tissue regeneration, the mechanism(s) by which topically applied FGF-2 induces angiogenesis in periodontal tissues has not been fully clarified. In this study, we investigated whether FGF-2 could induce vascular endothelial growth factor (VEGF)-A expression in periodontal ligament (PDL) cells and whether cell-to-cell interactions between PDL cells and endothelial cells could stimulate angiogenesis. FGF-2 induced VEGF-A secretion from MPDL22 cells (mouse periodontal ligament cell line) in a dose-dependent manner. Transwell and wound-healing assays revealed that co-stimulation with FGF-2 plus VEGF-A synergistically stimulated the migration of MPDL22 cells. Interestingly, co-culture of MPDL22 cells with bEnd5 cells (mouse endothelial cell line) also stimulated VEGF-A production from MPDL22 cells and tube formation by bEnd5 cells. Furthermore, time-lapse analysis revealed that MPDL22 cells migrated close to the tube-forming bEnd5 cells, mimicking pericytes. Thus, FGF-2 induces VEGF-A expression in PDL cells and induces angiogenesis in combination with VEGF-A. Cell-to-cell interactions with PDL cells also facilitate angiogenesis.

Royal jelly (RJ) has been reported to possess several physiological and pharmacological properties such as the ability to prevent osteoporosis in rats and anti-inflammatory effects. We hypothesized that RJ could have beneficial effects on the prevention or treatment of periodontal diseases, which are chronic inflammatory diseases caused by bacterial infection that result in resorption of the tooth-supporting bone. We assessed the effect of RJ on mineralization in mouse periodontal ligament cell clone 22 (MPDL22 cells), which are of an osteogenic and cementogenic lineage. The mRNA expression of osteopontin, osteocalcin and osterix, and mineralized nodule formation were significantly enhanced in RJ-treated MPDL22 cells. In addition, we investigated the effects of RJ on the production of inflammatory cytokines from MPDL22 cells stimulated with lipopolysaccharide (LPS) of Porphyromonas gingivalis, a periodontopathic bacterium. RJ suppressed LPS-induced interleukin-6 and CXC chemokine ligand 10 production from MPDL22 cells. Furthermore, RJ suppressed the expression of CD54 in MPDL22 cells: CD54 is the adhesion molecule involved in the accumulation of leukocytes in periodontal lesions. These findings suggest that the osteoinductive and anti-inflammatory effects of RJ can provide benefits for the treatment and prevention of periodontal diseases.

Reversible topographical changes were observed on a photochromic diarylethene microcrystalline film surface by alternate irradiation with UV and visible light. Two types of surfaces were prepared from this film: 1) Storage of the film at 30 °C for 24 hours in the dark after UV irradiation afforded a surface that was covered with needle-shaped crystals, whose diameter and length were approximately 1 μm and 10 μm, respectively, and showed a superhydrophobic lotus effect. 2) Storage of the film at 70 °C for 3 hours in the dark caused the needle-shaped crystals to be converted into larger rod-like crystals (5~8 μm wide and 20~30 μm long) by Ostwald ripening and a disappearance of the lotus effect. The obtained activation energy of the formation of the needle- and rod-shaped crystals was 143 and 162 kJ mol(-1), respectively. Subsequent UV irradiation to the surface, which was followed by storage at 50 °C for 1 hour in the dark, gave a doubly rough structure; small needle-shaped crystals were formed between the larger rod-shaped crystals. The surface showed both superhydrophobic properties and the pinned effect of the water droplet: the petal effect. Fractal analysis of both surfaces were carried out using a box-counting method, and the lotus effect was observed in the presence of smaller-sized crystals, whilst the petal effect was observed with larger sized crystals (ca. 100 μm). We demonstrated that the hydrophobic property was controlled by the distribution in crystal size of the closed-ring isomer of the diarylethene. Visible-light irradiation of both rough surfaces afforded surfaces with cubic-shaped micro-crystals of the open-ring isomer.

Antioxidative flavonoids are used to reduce the risk of cardiovascular diseases in humans. However, the precise mechanism for the anti-atherosclerotic actions of flavonoids remains to be elucidated. In the present study, to assess the mechanism for the action of antioxidative flavonoids on atherosclerosis, we investigated the effect of flavangenol, one of the most potent antioxidants currently known, on spontaneously hyperlipidemic B6.KOR-Apoeshl mice. Flavangenol was orally administered to B6.KOR-Apoeshl mice ad libitum (6 mg flavangenol/mouse/day). After 6 months, serum levels of lipids (total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol) and lipid peroxide were measured, and histopathological changes (lipid accumulation and inflammatory cell infiltration) in the aortic root were evaluated. Serum levels of total cholesterol and LDL-cholesterol were markedly increased, and HDL-cholesterol levels were decreased in B6.KOR-Apoeshl mice compared to C57BL/6 mice used as a control (p

Glucosamine, a naturally occurring amino monosaccharide, is widely used to treat osteoarthritis in humans. Furthermore, glucosamine exhibits an anti-inflammatory action by inhibiting the activation of neutrophils, chondrocytes and synoviocytes. Recently, we revealed that glucosamine suppresses cytokine-induced activation of intestinal epithelial cells in vitro. In the present study therefore, we investigated whether glucosamine exhibits the anti-inflammatory effect in vivo, using dextran sulfate sodium (DSS)-induced colitis in rats, a model of inflammatory bowel diseases (IBD). The results indicated that glucosamine improved the clinical symptoms (evaluated by disease activity index), and suppressed colonic inflammation (evaluated by colon length and weight/length ratio) and tissue injury (evaluated by histological damage score) in DSS-induced colitis. Furthermore, glucosamine inhibited the activation of intestinal epithelial cells, as evidenced by the suppressed phosphorylation of NF-kappaB in the intestinal mucosa of DSS-induced colitis. Collectively, these observations suggest that glucosamine is likely to suppress the activation of intestinal epithelial cells in vivo, thereby possibly exhibiting anti-inflammatory action in a DSS-induced rat colitis model. Thus, glucosamine could prove to be a useful agent for IBD.

Background: Angiopoietins, newly discovered vascular-specific growth factors, and vascular endothelial growth factors (VEGF) play distinct and complementary roles in angiogenesis and vascular maturation. However, the exact roles of angiogenic factors in the adult pulmonary vasculature remain unclear. Objective: To elucidate possible roles of angiopoietins and VEGF in the development of hypoxic pulmonary hypertension (PH), changes in the expression of angiogenic factors were examined. Methods: The cellular distribution and expression of angiopoietins and their receptor Tie2 and VEGF were investigated by RT-PCR, immunoblot, and immunohistochemical methods in rat lung under normal and hypoxic conditions. Results: During the development of PH with vascular remodeling characterized by a decrease in vessel density of intrapulmonary arteries, protein expression of angiopoietin-1 (Ang-1), Tie2, and VEGF significantly decreased in the pulmonary arteries, and Tie2 receptor was inactivated in the lung. The expression of angiopoietin-3 (Ang-3), an endogenous antagonist of Ang-1, significantly increased in the intima under hypoxic conditions. Conclusions: Since both Ang-1/Tie2 and VEGF promote angiogenesis and vascular survival, and play protective roles in the adaptation of microvascular changes during the onset of PH, the downregulation of both Ang-1/Tie2 and VEGF and upregulation of Ang-3 appear to be associated with vascular rarefaction and the development of hypoxic PH.

Herein, we report a new photoinduced change in surface morphology that provides superhydrophobic properties, obtained by the photoinduced reversible formation of fine fibril structures on coated microcrystalline surfaces. The origin of the reversible formation of fibrils is the photoisomerization of a photochromic diarylethene molecule 1 (see Scheme 1) of a thin film. The reversible changes in surface morphology of a thin film made from photochromic diarylethene 1 were followed by scanning electron microscopy (SEM), optical microscopy, and contact angle measurements of a water droplet. The film was prepared by coating a

Accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes ER overload, resulting in ER stress. To cope with ER stress, mammalian cells trigger a specific response known as the unfolded protein response (UPR). Although recent studies have indicated cross-talk between ER stress and oxidative stress, the mechanistic link is not fully understood. By using murine fibrosarcoma L929 cells, in which tumor necrosis factor (TNF) alpha induces accumulation of reactive oxygen species (ROS) and cell death, we show that TNFalpha induces the UPR in a ROS-dependent fashion. In contrast to TNFalpha, oxidative stresses by H2O2 or arsenite only induce eukaroytic initiation factor 2alpha phosphorylation, but not activation of PERK- or IRE1-dependent pathways, indicating the specificity of downstream signaling induced by various oxidative stresses. Conversely, the UPR induced by tunicamycin substantially suppresses TNFalpha-induced ROS accumulation and cell death by inhibiting reduction of cellular glutathione levels. Collectively, some, but not all, oxidative stresses induce the UPR, and pre-emptive UPR counteracts TNFalpha-induced ROS accumulation.

NF-kappaB downregulates tumor necrosis factor (TNF)-induced c-Jun N-terminal kinase (JNK) activation that promotes cell death, but the mechanism is not yet fully understood. By using murine embryonic fibroblasts (MEFs) that are deficient in TNF receptor-associated factor (TRAF) 2 and TRAF5 (DKO) or p65 NF-kappaB subunit (p65KO), we demonstrate here that TNF stimulation leads to accumulation of reactive oxygen species (ROS), which is essential for prolonged mitogen-activated protein kinase (MAPK) activation and cell death. Interestingly, dying cells show necrotic as well as apoptotic morphological changes as assessed by electron microscopy and flow cytometry, and necrotic, but not apoptotic, cell death is substantially inhibited by antioxidant. Importantly, TNF does not induce ROS accumulation or prolonged MAPK activation in wild-type MEFs, indicating that TRAF-mediated NF-kappaB activation normally suppresses the TNF-induced ROS accumulation that subsequently induces prolonged MAPK activation and necrotic cell death

A new family of indoaniline-derived calix[4]arenes has been synthesized for the purpose of developing a new chromogenic receptor. A condensing reaction of calix[4]arene (1) with 4-(diethylamino)-2-methylaniline hydrochloride (2) in the presence of an oxidizing agent under alkaline conditions affords mono- (3), 1,2-bis- (4), 1,3-bis- (5), and tetrakisindoaniline-derived (6) calix[4]arenes after careful column chromatography. Compound 3 is crystallized from a CHCl(3)-MeOH solution, and the crystal structure was determined by X-ray analysis. The crystal is monoclinic, space group P2(1)/n, Z = 4, a = 19.507(6) Å, b = 18.591(6) Å, c = 8.524(2) Å, beta = 94.69(2) degrees. The final R value for 2406 reflections of F(o)3sigma(F(o)) is 0.085. A unique intramolecular hydrogen-bonding network involving the carbonyl oxygen of indoaniline for 3 implied that the quinone carbonyl group as an acceptor of the chromophore can easily be subjected to an electrostatic interaction in the lower rim. Indeed, 1,3-bis(indoaniline)-derived 2,4-bis((ethoxycarbonyl)methoxy)calix[4]arene 7, prepared by the reaction of 5 with ethyl bromoacetate in the presence of NaH, is capable of undergoing an efficient ion-dipole interaction between the binding cation and the two quinone carbonyl groups of the chromophores, so that a selective Ca(2+)-induced pronounced color change (wavelength change100 nm) occurs with an association constant on the order of 10(6) in 99% EtOH, making 7 of potential use as an optical sensor for Ca(2+) detection. The IR and NMR studies have indicated that Ca(2+) is encapsulated in the cavity made by the distally located OCH(2)CO(2) groups on the lower rim of the cone-shaped calix[4]arene segment. Interestingly, however, the shape of the cavity in which Ca(2+) has been encapsulated does not have a C(2) axis of symmetry, as inferred from the (1)H-(1)H COSY experiment. On the other hand, 1,2-bis(indoaniline)-derived analogue 8 shows no response with metal ions, which can be interpreted to mean the absence of a cavity for encapsulation on the lower rim.

By alternate irradiation with UV and visible light, reversible topographical changes were observed. Step and valley formation while keeping the crystal confinement was observed below the glass transition temperature (Tg), while crystal growth via a softened state was observed above the Tg on the same diarylethene crystalline surface.

culture markedly decreased nuclear LXR protein levels, suggesting that 25HC3S may complex with LXR to prevent its activation. 25HC3S administration was followed by doseand timedependent decreases in SREBP-1 protein and mRNA, consistent with down regulation of SREBP-1 transcription. 25HC3S administration also led to a decrease in mature SREBP-1 accompanied by an increase in SREBP-1 precursor, consistent with post-translational downregulation of SREBP-1 activity. 25HC3S decreased the expression of a number of SREBP1-responsive genes including acetyl CoA carboxylase-1 (ACC-1) and fatty acid synthase (FAS), key enzymes involved in fatty acid biosynthesis, as well as Cyp7A1, HMGR, and LDLR, which are key proteins involved in cholesterol metabolism. 25HC, the precursor of 25HC3S, had opposite effects, increasing SREBP-1 and FAS mRNA levels in the hepatocytes. Conclusion: 25HC3S, initially produced in mitochondria in response to excess cholesterol, is a potent down-regulator of the cholesterol and fatty acid biosynthetic pathways. The effects of 25HC3S appear to be mediated via inhibition of LXR/SREBP-1 signaling.

C 11 H 12 O 6 N 2 crystallizes in P2 1 with a=11.434, b=10.456, c=4.7809A, β=94.43°, Z=2; R=0.042.