スルフォラファンの肝癌発育抑制効果および血管新生抑制効果に関する基礎的検討

Sulforaphane (SFN) exhibits inhibitory effects in different types of cancers. However, its inhibitory effect on liver cancer remains unknown. This study aimed to determine the therapeutic potential of SFN for the treatment of liver cancer and explore the functional mechanisms underlying the inhibitory effects of SFN. Water-Soluble Tetrazolium salt (WST-1) assay was performed to assess the in vitro effect of SFN on cell proliferation in the human liver cancer cell lines, HepG2 and Huh-7. The mRNA levels of Nrf2 target genes and cell cycle-related genes were determined using quantitative RT-PCR. For assessing the inhibitory effect of SFN in vivo, we injected immortalized liver cancer cells into BALB/c nude mice as a xenograft model. SFN was orally administrated daily after tumor inoculation and continued for thirty-five days until their sacrifices. Nrf2 activation, induced by SFN, was confirmed by mRNA upregulation of HO-1, MRP2, and NQO1 in both the cell lines. Significant inhibition of liver cancer cell proliferation by SFN was shown in vitro in a dose-dependent manner by the downregulation of CCND1, CCNB1, CDK1 and CDK2. In in vivo studies, the administration of SFN significantly reduced the subcutaneous tumor burdens at the end of experiments by suppressing tumor cell proliferation, confirmed by Ki67 immunohistochemical analysis. The mRNA levels of CCND1, CCNB1, CDK1 and CDK2 were also decreased in these SFNtreated xenograft tumors. Moreover, CD34 immunostaining elucidated that the intratumoral neovascularization was markedly attenuated in the SFN-treated xenograft tumors. SFN exerts inhibitory effect on human liver cancer cells with antiangiogenic activity. The earlier version of this study was presented at the meeting of AASLD Liver Learning on Oct 2017.博士（医学）・甲第707号・平成31年3月15日© The Author(s) 2018 Under License of Creative Commons Attribution 3.0 License https://creativecommons.org/licenses/by/3.0

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/)

Comparison of rhenium–porphyrin dyads for CO₂ photoreduction: photocatalytic studies and charge separation dynamics studied by time-resolved IR spectroscopy

We report a study of the photocatalytic reduction of CO₂ to CO by zinc porphyrins covalently linked to [ReI(2,2′-bipyridine)(CO)₃L]⁺/⁰ moieties with visible light of wavelength >520 nm. Dyad 1 contains an amide C₆H₄NHC(O) link from porphyrin to bipyridine (Bpy), Dyad 2 contains an additional methoxybenzamide within the bridge C₆H₄NHC(O)C₆H₃(OMe)NHC(O), while Dyad 3 has a saturated bridge C₆H₄NHC(O)CH₂; each dyad is studied with either L = Br or 3-picoline. The syntheses, spectroscopic characterisation and cyclic voltammetry of Dyad 3 Br and [Dyad 3 pic]OTf are described. The photocatalytic performance of [Dyad 3 pic]OTf in DMF/triethanolamine (5 : 1) is approximately an order of magnitude better than [Dyad 1 pic]PF₆ or [Dyad 2 pic]OTf in turnover frequency and turnover number, reaching a turnover number of 360. The performance of the dyads with Re–Br units is very similar to that of the dyads with [Re–pic]⁺ units in spite of the adverse free energy of electron transfer. The dyads undergo reactions during photocatalysis: hydrogenation of the porphyrin to form chlorin and isobacteriochlorin units is detected by visible absorption spectroscopy, while IR spectroscopy reveals replacement of the axial ligand by a triethanolaminato group and insertion of CO₂into the latter to form a carbonate. Time-resolved IR spectra of [Dyad 2 pic]OTf and [Dyad 3 pic]OTf (560 nm excitation in CH₂Cl₂) demonstrated electron transfer from porphyrin to Re(Bpy) units resulting in a shift of ν(CO) bands to low wavenumbers. The rise time of the charge-separated species for [Dyad 3 pic]OTf is longest at 8 (±1) ps and its lifetime is also the longest at 320 (±15) ps. The TRIR spectra of Dyad 1 Br and Dyad 2 Br are quite different showing a mixture of 3MLCT, IL and charge-separated excited states. In the case of Dyad 3 Br, the charge-separated state is absent altogether. The TRIR spectra emphasize the very different excited states of the bromide complexes and the picoline complexes. Thus, the similarity of the photocatalytic data for bromide and picoline dyads suggests that they share common intermediates. Most likely, these involve hydrogenation of the porphyrin and substitution of the axial ligand at rhenium

Molecular characterization of the CRa gene conferring clubroot resistance in Brassica rapa

Clubroot disease is one of the major diseases affecting Brassicaceae crops, and a number of these crops grown commercially, such as Chinese cabbage (Brassica rapa L. ssp. pekinensis), are known to be highly susceptible to clubroot disease. To provide protection from this disease, plant breeders have introduced genes for resistance to clubroot from the European turnip into susceptible lines. The CRa gene confers specific resistance to the clubroot pathogen Plasmodiophora brassicae isolate M85. Fine mapping of the CRa locus using synteny to the Arabidopsis thaliana genome and partial genome sequences of B. rapa revealed a candidate gene encoding a TIR-NBS-LRR protein. Several structural differences in this candidate gene were found between susceptible and resistant lines, and CRa expression was observed only in the resistant line. Four mutant lines lacking clubroot resistance were obtained by the UV irradiation of pollen from a resistant line, and all of these mutant lines carried independent mutations in the candidate TIR-NBS-LRR gene. This genetic and molecular evidence strongly suggests that the identified gene is CRa. This is the first report on the molecular characterization of a clubroot Resistance gene in Brassicaceae and of the disease resistance gene in B. rapa.ArticlePLANT MOLECULAR BIOLOGY. 80(6):621-629 (2012)journal articl

Combustion characteristics of Mg vapor jet flames in CO2 atmospheres

An experimental study was performed on the combustion characteristics of a jet diffusion flame of Mg vapor injected through a small nozzle into CO2 atmospheres at low pressures from 8 to 48 kPa with a view to using Mg as fuel for a CO2-breathing turbojet engine in the Mars atmosphere. The Mg vapor jet produced three types of the flame. At lower pressures and higher injection velocities, a red-heated jet flame formed, in which the injected Mg vapor was heated by spontaneous reactions, turning red. At medium pressures and injection velocities, a stable luminous lifted-like flame developed above the rim of the chimney, a tube-like combustion product for the Mg vapor passage that grew on the nozzle during combustion. The flame had similar flame length properties to laminar jet diffusion flames of gaseous fuels. At higher pressures and lower injection velocities, a stable luminous attached flame developed at the rim of the chimney. The same reactions, producing MgO(g), CO and MgO(c), proceeded preferentially for all flames and chimneys. Carbon was only subordinately generated. Burning behavior of Mg vapor jets in a CO2 atmosphere has been represented, including the homogeneous reaction of Mg vapor with CO2, the diffusion of CO2, and the condensation and deposit of MgO. The injection velocity of Mg vapor at the rim of the chimney and the exothermic reactions with diffused CO2 that occur there play a crucial role in the attachment and development of the flames. The flame structure may be explained in terms of the relatively low gas-phase reaction rate of Mg with CO2

What Affects Chinese Households’ Behavior in Sorting Solid Waste? A Case Study from Shanghai, Shenyang, and Chengdu

The main aim of this study was to examine residents’ environmental behavior in sorting solid household waste, and to identify the integrative factors that contribute to their waste-separation cooperation and other related pro-environmental behaviors. This was achieved based on a questionnaire survey in Shenyang, Chengdu, and Shanghai. Methodologically, we applied a discrete choice model to examine whether individuals’ garbage sorting behaviors differ based on their characteristics, social attributes, residential circumstances, and environmental awareness, and whether these factors are correlated with individuals’ receptiveness to a refuse charge system, or to policies requiring garbage sorting. We further examined whether individuals’ garbage sorting behavior, their receptiveness to fee-based waste collection, and their receptiveness to policies requiring garbage sorting differ across areas. In this particular survey, we introduced a 16 item scale of pro-environmental behavior and a nine item scale of altruism to ascertain the ways in which internal motivational factors affect people’s environmentally conscious voluntary behavior. Overall, the present work is expected to contribute to an important understanding of the motivational forces and incentives behind human pro-environmental behavior and action. It also brings relevance to the analysis of moral solidarity in relation to the household waste disposal problems currently confronting us today

Particle filters for partially-observed diffusions.

In this paper we introduce novel particle filters for a class of partially-observed continuous-time dynamic models where the signal is given by a multivariate diffusion process. We consider a variety of observation schemes, including diffusion observed with error, observation of a subset of the components of the multivariate diffusion and arrival times of a Poisson process whose intensity is a known function of the diffusion (Cox process). Unlike currently available methods, our particle filters do not require approximations of the transition and/or the observation density using time-discretisations. Instead, they build on recent methodology for the exact simulation of the diffusion process and the unbiased estimation of the transition density as described in Beskos et al. (2006). In particular, we introduce the Generalised Poisson Estimator, which generalises the Poisson Estimator of Beskos et al. (2006). Thus, our filters avoid the systematic biases caused by time-discretisations and they have significant computational advantages over alternative continuous-time filters. These advantages are supported theoretically by a central limit theorem