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Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

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World j.urnal of Gastroenterology 2024年第28期30卷 3428-3446页

作者： Aritoshi Koizumi Kosuke Kaj. Norihisa nishimura Shohei Asada Takuya Matsuda Misako Tanaka Nobuyuki Yorioka Yuki Tsuj. Koh Kitagawa Shinya Sato Tadashi Namisaki Takemi Akahane Hitoshi Yoshij. Department of Gastroenterology Nara Medical UniversityKashihara 634-8521Japan

BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver *** proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are maj.r contributors to the pathological progression of ***,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary ***,the benefits of EFN for ALD treatment is *** To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse *** ALD-related liver fibrosis was induced in female C57BL/6j.mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally inj.cting carbon tetrachloride thrice weekly(1 mL/kg)for 8 ***(3 and 10 mg/kg/day)was orally administered during the experimental *** and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier *** EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based *** The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN *** promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARα***,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)*** improved intestinal hyperpermeability by restoring tight j.nction proteins and autophagy and by inhibiting apoptosis and proinflammatory *** protective effect on intestinal bar

关键词： Liver fibrosis Ethanol Gut barrier function Apoptosis Autophagy Peroxisome proliferator activated receptor

High-precision transfer-printing and integration of vertically oriented semiconductor arrays for flexible device fabrication

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Nano Research 2014年第7期7卷 998-1006页

作者： Mark Triplett Hideki nishimura Matthew Ombaba V. j. Logeeswarren Matthew Yee Kazim G. Polat j.n Y. Oh Takashi Fuyuki Francois Leonard M. Saif Islam Center for Nano and Micro Manufacturing and Department of Electrical and Computer Engineering University of California Davis CA 95616 USA Department of Physics University of California Davis CA 95515 USA Sandia National Laboratories Livermore CA 94551 USA Microelectronic Device Science Laboratory Nara Institute of Science and Technology Japan

Flexible electronics utilizing single crystalline semiconductors typically require post-growth processes to assemble and incorporate the crystalline materials onto flexible substrates. Here we present a high-precision transfer-printing method for vertical arrays of single crystalline semiconductor materials with widely varying aspect ratios and densities enabling the assembly of arrays on flexible substrates in a vertical fashion. Complementary fabrication processes for integrating transferred arrays into flexible devices are also presented and characterized. Robust contacts to transferred silicon wire arrays are demonstrated and shown to be stable under flexing stress down to bending radii of 20 mm. The fabricated devices exhibit a reversible tactile response enabling silicon based, nonpiezoelectric, and flexible tactile sensors. The presented system leads the way towards high-throughput, manufacturable, and scalable fabrication of flexible devices.

关键词： transfer printing nanowires flexible electronics printable electronics nanoscale devices

Computational Analysis of Theacrine, a Purported Nootropic and Energy-Enhancing Nutritional Supplement

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Computational Chemistry 2019年第1期7卷 27-37页

作者： Bradley O. Ashburn Diana j. Le Corin K. nishimura Mathematics and Natural Sciences Division University of Hawaii-Leeward Community College Pearl City HI USA

Herein is the first reported conceptual density functional theory (DFT) investigation of the purine alkaloid theacrine and the comparison of quantum chemical properties to the closely related stimulant caffeine. DFT global chemical reactivity descriptors (chemical hardness/softness, chemical potential/ electronegativity, and electrophilicity) and local reactivity descriptors (Fukui functions and dual descriptor) were calculated for both compounds using Spartan ‘16 software. All calculations were carried out at the B3LYP/6-31G* level of theory. Reactivity analysis of the Fukui dual descriptor calculations reveals sites of nucleophilic and electrophilic attack. The results provide a solid chemical foundation for understanding how theacrine interacts with cellular systems.

关键词： Theacrine Caffeine Density Functional Theory Computational Analysis

Treatment of a densely fused fissure during thoracoscopic right middle lobectomy

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Open j.urnal of Pediatrics 2013年第2期3卷 105-107页

作者： Hiroyuki Koga Kenj. Suzuki Tadaharu Okazaki Kinya nishimura Geoffrey j. Lane Atsuyuki Yamataka Department of Anesthesiology Juntendo University School of Medicine Tokyo Japan Department of Pediatric General and Urogenital Surgery Juntendo University School of Medicine Tokyo Japan Department of Thoracic General Surgery Juntendo University School of Medicine Tokyo Japan

Aim: To report a case of fused fissure between the right upper and middle lobes that we treated using a surgical stapler rather than a Ligasure device for the benefit of creating a better division between the right upper and middle lobes and to effectively seal the lung parenchyma. Case: A 2-year-old girl with congenital cystic adenomatoid malformation of the right middle lobe (RML) was referred to our institution for further management after a series of infections. The vein of the RML, which drains into the superior pulmonary vein, was isolated and divided using endoclips. The bronchus was then exposed and divided using endo-clips. The arteries of the RML could be identified and ligated, allowing a line demarcating the maj.r fissure to be identified and dissected. A stapler device was then used to seal the lung parenchyma and create a division between the right upper and middle lobes. She is currently well after follow-up of 16 months, with no episodes of respiratory distress or recurrence of symptoms. Conclusion: Our technique for dividing the pulmonary vein, then the bronchus, then the pulmonary artery and finally the fused fissure is safe and could be applied whenever fused fissures are encountered during thoracoscopic pulmonary lobectomy.

关键词： Thoracoscopic Surgery Pulmonary Lobectomy Fused Fissure Surgical Stapler

Nicotinamide Adenine Dinucleotide and Adenosine Triphosphate Oscillations Caused by Gradual Entry of Substrates within Mitochondria

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j.urnal of Biophysical Chemistry 2022年第2期13卷 13-28页

作者： Taketoshi Hideshima Mikie nishimura j.F. Oberlin University Tokyo Japan

Nicotinamide adenine dinucleotide (NAD) oscillation was observed when the isolated mitochondria were immersed in a pyruvate solution. In addition, when an adenosine diphosphate (ADP) was added to the mitochondrial suspension containing pyruvate, adenosine triphosphate (ATP) oscillation was observed as well as NADH oscillation. At this time, the pH within mitochondria also oscillated. It was found that the oscillatory reaction of NADH caused by the membrane permeation of pyruvate continues, causing the oscillation of NADH and H+ in the subsequent reactions. The pH oscillation led to the ATP oscillation. It is considered that the oscillatory reaction caused by the gradual entry of pyruvate into mitochondria was thought to be carried over to both the citric acid cycle and the respiratory chain, ultimately leading to the ATP oscillation in oxidative phosphorylation. Similarly, it was found that membrane permeation of malate causes the gradual occurrence of NADH, at which point NADH oscillates, followed by an oscillatory reaction of the respiratory chain, and finally ATP oscillation. It was found that the oscillations of NADH and ATP occur without going through the citric acid cycle. Oscillations of NADH and other intermediates in both the citric acid cycle and respiratory chain were also confirmed by experiments using semipermeable membranes. These results support our hypothesis that the gradual entry of the substrate by membrane permeation triggers an oscillatory reaction of the enzyme, which is also carried over to subsequent reactions.

关键词： Adenosine Triphosphate Oscillation Nicotinamide Adenine Dinucleotide Oscillation Mitochondria Membrane Permeation

Study of Proton Resonances in ^(22)Mg by Resonant Elastic Scattering of ^(21)Na+p and Its Astrophysical Implication in ^(18)Ne(α,p) ^(21)Na Reaction Rate

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原子核物理评论 2009年第S1期26卷 153-157页

作者： S.Kubono T.Teranishi M.Notani H.Baba S.nishimura j.Y.Moon M.nishimura S.Michimasa H.Iwasaki Y.Yanagisawa N.Hokoiwa M.Kibe j.H.Lee S.Kato Y.Gono C.S.Lee Center for Nuclear Study University of Tokyo(CNS) Department of Physics Kyushu University RIKEN(The Institute of Physical and Chemical Research) Department of Physics Chung-Ang University Department of Physics Yamagata University

Proton resonant states in 22Mg have been investigated by the resonant elastic scattering of 21Na+p. The 21Na beam with a mean energy of 4.00 MeV/u was separated by the CNS radioactive ion beam separator(CRIB) and bombarded a thick(CH2)n target. The energy spectra of recoiled protons were measured at scattering angles of θcm ≈172° and 146°,respectively. A new state at 7.06 MeV has been observed clearly and another new one at 7.28 MeV is tentatively identified due to its low statistics. The proton resonant parameters were deduced from an R-matrix analysis of the differential cross section data. The astrophysical resonant reaction rate for the 18Ne(α,p)21Na reaction has been estimated,and it is about five times larger than that assumed before.

关键词： nuclear astrophysics reaction rate nuclear structure and property

Nuclear structure of proton-rich unstable nucleus ^(28)P studied by g-factor measurement

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Chinese Physics C 2009年第S1期33卷 215-217页

作者：郑永男周冬梅 K. Matsuta M. Mihara M. Fukuda D. nishimura j. Komurasaki D. Ishikawa R. Matsumiya T. Nagatomo T. Izumikawa S. Takahashi H. Hirano T. Ohtsubo S. Momota Y. Noj.ri A. Kitagawa M. Kanazawa M. Torikoshi S. Sato T. Minamisono j. R. Alonso G. F. Krebs T. j. M. Symons 袁大庆左翼范平 T. Suzuki 张锡珍朱升云 China Institute of Atomic Energy Department of Physics Osaka University RIKEN Wako Saitama 351-0198 Japan RI Center Niigata University Department of Physics Niigata University Kochi University of Technology National Institute of Radiological Sciences Inage-ku Chiba 263-8555 Japan Fukui University of Technology Lawrence Berkeley Laboratory Department of Physics Nihon University

Nuclear structure of proton-rich unstable nucleus 28P has been studied by measuring its g-factor for the first time. The g-factor of 28P (Iπ =3+, T1/2=270.3 ms) was measured by means of β-NMR technique combined with the new polarization technique for charge exchange reaction product in the intermediate energy heavy ion collisions. The obtained g-factor of g=0.1028(27) is very much quenched from the Schmidt value, but is well reproduced by the shell model (+0.102). In connection with the magnetic moment of the mirror partner and the β-ray transition probability, the orbital angular momenta and intrinsic spins of protons and neutrons have been determined as lp =0.43(29), ln =1.85(29), Sp)=0.28(4), and Sn =0.44(4).

关键词： 28P β-NMR nuclear magnetic moment exotic nuclei

Dual therapy with zinc acetate and rifaximin prevents from ethanolinduced liver fibrosis by maintaining intestinal barrier integrity

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World j.urnal of Gastroenterology 2021年第48期27卷 8323-8342页

作者： Yuki Fuj.moto Kosuke Kaj. Norihisa nishimura Masahide Enomoto Koj. Murata Soichi Takeda Hiroaki Takaya Hideto Kawaratani Kei Moriya Tadashi Namisaki Takemi Akahane Hitoshi Yoshij. Department of Gastroenterology Nara Medical UniversityKashihara 6348521NaraJapan

BACKGROUND Hepatic overload of gut-derived lipopolysaccharide dictates the progression of alcoholic liver disease(ALD)by inducing oxidative stress and activating Kupffer cells and hepatic stellate cells through toll-like receptor 4 ***,targeting the maintenance of intestinal barrier integrity has attracted attention for the treatment of *** acetate and rifaximin,which is a nonabsorbable antibiotic,had been clinically used for patients with cirrhosis,particularly those with hepatic encephalopathy,and had been known to improve intestinal barrier ***,only few studies focused on their efficacies in preventing the ALD-related fibrosis *** To investigate the effects of a combined zinc acetate with rifaximin on liver fibrosis in a mouse ALD *** To induce ALD-related liver fibrosis,female C57BL/6j.mice were fed a 2.5%(v/v)ethanol-containing Lieber-DeCarli liquid diet and received intraperitoneal carbon tetrachloride(CCl4)inj.ction twice weekly(1 mL/kg)for 8 *** acetate(100 mg/L)and/or rifaximin(100 mg/L)were orally administered during experimental *** steatosis,inflammation and fibrosis as well as intestinal barrier function were evaluated by histological and molecular ***,the direct effects of both agents on Caco-2 barrier function were assessed by in vitro *** the ethanol plus CCl4-treated mice,combination of zinc acetate and rifaximin attenuated oxidative lipid peroxidation with downregulation of Nox2 and *** combination significantly inhibited the Kupffer cells expansion and the proinflammatory response with blunted hepatic exposure of lipopolysaccharide and the toll-like receptor 4/nuclear factor kB ***,liver fibrosis and hepatic stellate cells activation were efficiently suppressed with downregulation of Mmp-2,-9,-13,and *** agents improved the atrophic changes and permeability in the ileum,with restoration of tight j.nction proteins(Tj.s)

关键词： Liver fibrosis Intestinal permeability Alcoholic liver disease Lipopolysaccharide Toll-like receptor Tight j.nction protein

ICRF Heated Long-Pulse Plasma Discharges in LHD

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Plasma Science and Technology 2006年第1期8卷 28-32页

作者： R. KUMAZAWA T. SEKI T. MUTOH K. SAITO T. WATARI Y. NAKAMURA M. SAKAMOTO T. WATANABE S. KUBO T. SHIMOZUMA Y. YOSHIMURA H. IGAMI Y. TAKEIRI Y. OKA K. TSUMORI M. OSAKABE K. IKEDA K. NAGAOKA O. KANEKO j. MIYAZAWA S. MORITA K. NARIHARA M. SHOj. S. MASUZAKI M. GOTO T. MORISAKI B. j. PETERSON K. SATO T. TOKUZAWA N. ASHIKAWA K. nishimura H. FUNABA H. CHIKARAISHI T. NOTAKE Y. TORII H. OKADA M. ICHIMURA H. HIGAKI Y. TAKASE H. KASAHARA F. SHIMPO G.NOMURA C.TAKAHASHI M.YOKOTA A. KATO 赵燕平 j. S. YOON j. G. KWAK H. YAMADA K. KAWAHATA N. OHYABU K. IDA Y. NAGAYAMA N. NODA A. KOMORI S. SUDO O. MOTOj.MA National Institute for Fusion Science Toki Japan Kyusyu University Kasuga Japan Nagoya University Faculty of Engineering Nagoya Japan Kyoto University Institute of Advanced Energy Uji Japan Tsukuba University Plasma Research Center Tsukuba Japan Tokyo University Graduate School of Frontier Sciences Tokyo Japan Institute of Plasma Physics Chinese Academy of Sciences Hefei 230031 China KAERI 150 Deogjin-dong Yuseong-gu Daejeon Korea Rep.

A long-pulse plasma discharge for more than 30 min. was achieved on the Large Helical Device （LHD）. A plasma of ne = 0.8 × 10^19 m^-3 and T10 = 2.0 keV was sustained with PICH = 0.52 MW, PECH = 0.1 MW and averaged PNBI = 0.067 MW. Total inj.cted heating energy was 1.3 G j. which was a quarter of the prepared RF heating energy. One of the keys to the success of the experiment was a dispersion of the local plasma heat load to divertors, accomplished by shifting the magnetic axis inward and outward.

关键词： helical/stellarator configuration ICRF heating steady state operation