Pole inflation in Jordan frame supergravity

We investigate inflation models in Jordan frame supergravity, in which an inflaton non-minimally couples to the scalar curvature. By imposing the condition that an inflaton would have the canonical kinetic term in the Jordan frame, we construct inflation models with asymptotically flat potential through pole inflation technique and discuss their relation to the models based on Einstein frame supergravity. We also show that the model proposed by Ferrara et al. has special position and the relation between the K\"ahler potential and the frame function is uniquely determined by requiring that scalars take the canonical kinetic terms in the Jordan frame and that a frame function consists only of a holomorphic term (and its anti-holomorphic counterpart) for symmetry breaking terms. Our case corresponds to relaxing the latter condition.Comment: 27 pages, 1 figure; revised version of the manuscript, accepted for publication in JCA

L-カルニチンとアンギオテンシン-II1型受容体遮断薬の組み合わせは、非アルコール性脂肪肝炎ラットモデルにおける肝線維症に有益な効果を有する

Inflammation and oxidative stress contribute to the progression of nonalcoholic steatohepatitis (NASH). Hepatic fibrosis and activated hepatic stellate cells (Ac-HSCs) are attenuated by Angiotensin-II type 1 Receptor Blocker (ARB), and L-carnitine is effective for NASH by ameliorating oxidative stress, but neither agent is effective in a clinical setting. We evaluated the effect of the combination of L-carnitine and ARB on liver fibrosis using a rat NASH model. A Choline-Deficient/L-Amino Acid-defined (CDAA) diet was fed to F344 rats for 8 weeks. The rats were then divided into a control group, group receiving L-carnitine or ARB alone, and group receiving L-carnitine plus ARB. Therapeutic efficacy was assessed by evaluating liver fibrosis, liver fatty acid metabolism, and oxidative stress. ARB inhibited liver-specific tumor necrotic factor-α and LPS-binding protein, which are involved in hepatic inflammation. L-Carnitine reduced hepatic oxidative stress by rescuing hepatic sterol-regulatory elementbinding protein 1 and thiobarbituric acid reactive substances induced by the CDAA diet. Combination of L-carnitine and ARB improved liver fibrosis, with concomitant HSC suppression. Therefore, we suggest that L-carnitine and ARB are effective in suppressing liver fibrosis. Currently both drugs are in clinical use, and a combination of the two could be an effective therapy for NASH fibrosis.博士（医学）・甲第736号・令和2年3月16日Copyright © 2019 Hideto Kawaratani, Biomed J Sci & Tech Res. This is an openaccess article distributed under the terms of the Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/)

エスジーエルティー2阻害薬（カナグリフロジン）およびジペプチジルペプチダーゼ４阻害薬（テネリグリプチン）との併用療法は非糖尿病ラットモデルにおける非アルコール性脂肪肝炎の進行を抑制する

Hepatocellular carcinoma (HCC) is the strongest independent predictor of mortality in non-alcoholic steatohepatitis (NASH)-related cirrhosis. The effects and mechanisms of combination of sodium-dependent glucose cotransporter inhibitor and canagliflozin (CA) and dipeptidyl peptidase-4 inhibitor and teneligliptin (TE) on non-diabetic NASH progression were examined. CA and TE suppressed choline-deficient, L-amino acid-defined diet-induced hepatic fibrogenesis and carcinogenesis. CA alone or with TE significantly decreased proinflammatory cytokine expression. CA and TE significantly attenuated hepatic lipid peroxidation. In vitro studies showed that TE alone or with CA inhibited cell proliferation and TGF-β1 and α1 (I)-procollagen mRNA expression in Ac-HSCs. CA+TE inhibited liver fibrogenesis by attenuating hepatic lipid peroxidation and inflammation and by inhibiting Ac-HSC proliferation with concomitant attenuation of hepatic lipid peroxidation. Moreover, CA+TE suppressed in vivo angiogenesis and oxidative DNA damage. CA or CA+TE inhibited HCC cells and human umbilical vein endothelial cell (HUVEC) proliferation. CA+TE suppressed vascular endothelial growth factor expression and promoted increased E-cadherin expression in HUVECs. CA+TE potentially exerts synergistic effects on hepatocarcinogenesis prevention by suppressing HCC cell proliferation and angiogenesis and concomitantly reducing oxidative stress and by inhibiting angiogenesis with attenuation of oxidative stress. CA+TE showed chemopreventive effects on NASH progression compared with single agent in non-diabetic rat model of NASH, concurrent with Ac-HSC and HCC cell proliferation, angiogenesis oxidative stress, and inflammation. Both agents are widely, safely used in clinical practice; combined treatment may represent a potential strategy against NASH.博士（医学）・甲第765号・令和3年3月15日© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

肝線維化に対するファルネソイドX受容体アゴニストとジペプチジルペプチダーゼ-4阻害薬の併用効果

Aim: Non-alcoholic steatohepatitis (NASH) has a broad clinicopathological spectrum (inflammation to severe fibrosis). The farnesoid X receptor agonist obeticholic acid (OCA) ameliorates the histological features of NASH; satisfactory antifibrotic effects have not yet been reported. Here, we investigated the combined effects of OCA + a dipeptidyl peptidase-4 inhibitor (sitagliptin) on hepatic fibrogenesis in a rat model of NASH. Methods: Fifty Fischer 344 rats were fed a choline-deficient L-amino-acid-defined (CDAA) diet for 12 weeks. The in vitro and in vivo effects of OCA + sitagliptin were assessed along with hepatic fibrogenesis, lipopolysaccharide-Toll-like receptor 4 (TLR4) regulatory cascade and intestinal barrier function. Direct inhibitory effects of OCA + sitagliptin on activated hepatic stellate cells (Ac-HSCs) were assessed in vitro. Results: Treatment with OCA + sitagliptin potentially inhibited hepatic fibrogenesis along with Ac-HSC proliferation and hepatic transforming growth factor (TGF)-β1, α1(I)-procollagen, and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expression and hydroxyproline levels. Obeticholic acid inhibited hepatic TLR4 expression and increased hepatic matrix metalloproteinase-2 expression. Obeticholic acid decreased intestinal permeability by ameliorating CDAA diet-induced zonula occludens-1 disruption, whereas sitagliptin directly inhibited Ac-HSC proliferation. The in vitro suppressive effects of OCA + sitagliptin on TGF-β1 and α1(I)-procollagen mRNA expression and p38 phosphorylation in Ac-HSCs were almost consistent. Sitagliptin directly inhibited the regulation of Ac-HSC. Conclusions: Treatment with OCA + sitagliptin synergistically affected hepatic fibrogenesis by counteracting endotoxemia induced by intestinal barrier dysfunction and suppressing Ac-HSC proliferation. Thus, OCA + sitagliptin could be a promising therapeutic strategy for NASH.博士（医学）・甲第737号・令和2年3月16日© 2019 The Japan Society of HepatologyThis is the peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1111/hepr.13385], which has been published in final form at [https://doi.org/10.1111/hepr.13385]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

Synthesis and Unique Optical Properties of Selenophenyl BODIPYs and Their Linear Oligomers

A series of selenophene-substituted boron-dipyrrin (BODIPY) monomers and selenophene-linked BODIPY oligomers was synthesized. The synthesized BODIPYs show good absorption/emission properties in the red to near-infrared region. Furthermore, some of the selenophenyl BODIPYs are not only useful fluorophores but also good photosensitizers to produce singlet oxygen

Synthesis of Daidzein Glycosides, α-Tocopherol Glycosides, Hesperetin Glycosides by Bioconversion and Their Potential for Anti-Allergic Functional-Foods and Cosmetics

Daidzein is a common isoflavone, having multiple biological effects such as anti-inflammation, anti-allergy, and anti-aging. α-Tocopherol is the tocopherol isoform with the highest vitamin E activity including anti-allergic activity and anti-cancer activity. Hesperetin is a flavone, which shows potent anti-inflammatory effects. These compounds have shortcomings, i.e., water-insolubility and poor absorption after oral administration. The glycosylation of bioactive compounds can enhance their water-solubility, physicochemical stability, intestinal absorption, and biological half-life, and improve their bio- and pharmacological properties. They were transformed by cultured Nicotiana tabacum cells to 7-β-glucoside and 7-β-gentiobioside of daidzein, and 3′- and 7-β-glucosides, 3′,7-β-diglucoside, and 7-β-gentiobioside of hesperetin. Daidzein and α-tocopherol were glycosylated by galactosylation with β-glucosidase to give 4′- and 7-β-galactosides of daidzein, which were new compounds, and α-tocopherol 6-β-galactoside. These nine glycosides showed higher anti-allergic activity, i.e., inhibitory activity toward histamine release from rat peritoneal mast cells, than their respective aglycones. In addition, these glycosides showed higher tyrosinase inhibitory activity than the corresponding aglycones. Glycosylation of daidzein, α-tocopherol, and hesperetin greatly improved their biological activities

Synthesis and Unique Optical Properties of Selenophenyl BODIPYs and Their Linear Oligomers

A series of selenophene-substituted boron-dipyrrin (BODIPY) monomers and selenophene-linked BODIPY oligomers was synthesized. The synthesized BODIPYs show good absorption/emission properties in the red to near-infrared region. Furthermore, some of the selenophenyl BODIPYs are not only useful fluorophores but also good photosensitizers to produce singlet oxygen