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Hepatic reconstruction from fetal porcine liver cells using a radial flow bioreactor

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World Journal of Gastroenterology 2008年第17期14卷 2740-2747页

作者： Yuji Ishii Ryota Saito Hideki Marushima Ryusuke ito Taro Sakamoto Katsuhiko Yanaga Department of Surgery the Jikei University School of Medicine

AIM： To examine the efficacy of the radial flow bioreactor （RFB） as an extracorporeal bioartificial liver （BAL） and the reconstruction of liver organoids using embryonic pig liver cells. METHODS： We reconstructed the liver organoids using embryonic porcine liver cells in the RFB. We also determined the gestational time window for the optimum growth of embryonic porcine liver cells. Five weeks of gestation was designated as embryonic day （E） 35 and 8 wk of gestation was designated as E56. These cells were cultured for one week before morphological and functional examinations. Moreover, the efficacy of pulsed adminisbation of a high concentration hepatocyte growth factor （HGF） was examined. RESULTS： Both cell growth and function were excellent after harvesting on E35. The pulsed administration of a high concentration of HGF promoted the differentiation and maturation of these fetal hepatic cells. Microscopic examination of organoids in the RFB revealed palisading and showed that bile duct-like structures were well developed, indicating that the organoids were mini livers. Transmission electron microscopy revealed microvilli on the luminal surfaces of bile duct-like structures and junctional complexes, which form the basis of the cytoskeleton of epithelial tissues. Furthermore, strong expression of connexin （Cx） 32, which is the main protein of hepatocyte gap junctions, was observed. With respect to liver function, ammonia detoxification and urea synthesis were shown to be performed effectively. CONCLUSION： Our system can potentially be applied in the fields of BAL and transplantation medicine.

关键词： Liver organoid Radial flow bioreactor Bioartificial liver Fetal porcine liver Hepatocyte growthfactor

Lysophosphatidic acid induced nuclear translocation of nuclear factor-κB in Panc-1 cells by mobilizing cytosolic free calcium

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World Journal of Gastroenterology 2008年第28期14卷 4473-4479页

作者： Yoshiyuki Arita Tetsuhide ito Takamasa Oono Ken Kawabe Terumasa Hisano Ryoichi Takayanagi Department of Medicine and Bioregulatory Science Graduate School of Medical SciencesKyushu UniversityFukuoka 812-8582Japan

AIM: To clarify whether Lysophosphatidic acid (LPA) activates the nuclear translocation of nuclear factor-κB (NF-κB) in pancreatic cancer. METHODS: Panc-1, a human pancreatic cancer cell line, was used throughout the study. The expression of LPA receptors was confirmed by reverse-transcript polymerase chain reaction (RT-PCR). Cytosolic free calcium was measured by fluorescent calcium indicator fura-2, and the localization of NF-κB was visualized by immunofluorescent method with or without various agents, which effect cell signaling. RESULTS: Panc-1 expressed LPA receptors, LPA1, LPA2 and LPA3. LPA caused the elevation of cytosolic free calcium dose-dependently. LPA also caused the nuclear translocation of NF-κB. Cytosolic free calcium was attenuated by pertussis toxin (PTX) and U73122, an inhibitor of phospholipase C. The translocation of NF-κB was similarly attenuated by PTX and U73122, but phorbol ester, an activator of protein kinase C, alone did not translocate NF-κB. Furthermore, the translocation of NF-κB was completely blocked by Ca2+ chelator BAPTA-AM. Thapsigargin, an endoplasmic- reticulum Ca2+-ATPase pump inhibitor, also promoted the translocation of NF-κB. Staurosporine, a proteinkinase C inhibitor, attenuated translocation of NF-κB induced by LPA. CONCLUSION: These findings suggest that protein kinase C is activated endogenously in Panc-1, and protein kinase C is essential for activating NF-κB with cytosolic calcium and that LPA induces the nuclear translocation of NF-κB in Panc-1 by mobilizing cytosolic free calcium.

关键词： Lysophosphatidic acid Nuclear translocation Nuclear factor-κB Cytosolic free calcium Panc-1

Randomized controlled trial of pancreatic stenting to prevent pancreatitis after endoscopic retrograde cholangiopancreatography

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World Journal of Gastroenterology 2012年第14期18卷 1635-1641页

作者： Yoshiaki Kawaguchi Masami Ogawa Fumio Omata Hiroyuki ito Tooru Shimosegawa Tetsuya Mine Division of Gastroenterology Tokai University School of MedicineIsehara 259-1193Japan Division of Gastroenterology Tohoku University Graduate School of Medicine1-1 Seiryo-machiAobakuSendai CityMiyagi 980-8574Japan

AIM:To determine the effectiveness of pancreatic duct(PD) stent placement for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography(ERCP) in high risk ***:Authors conducted a single-blind,randomized controlled trial to evaluate the effectiveness of a pancreatic spontaneous dislodgement stent against post-ERCP pancreatitis,including rates of spontaneous dislodgement and *** defined high risk patients as having any of the following:sphincter of Oddi dysfunction,difficult cannulation,prior history of post-ERCP pancreatitis,pre-cut sphincterotomy,pancreatic ductal biopsy,pancreatic sphincterotomy,intraductal ultrasonography,or a procedure time of more than 30 *** were randomized to a stent group(n = 60) or to a non-stent group(n = 60).An abdominal radiograph was obtained daily to assessspontaneous stent ***-ERCP pancreatitis was diagnosed according to consensus ***:The mean age(± standard deviation) was 67.4 ± 13.8 years and the male:female ratio was 68:*** the stent group,the mean age was 66 ± 13 years and the male:female ratio was 33:27,and in the non-stent group,the mean age was 68 ± 14 years and the male:female ratio was 35:*** were no significant differences between groups with respect to age,gender,final diagnosis,or type of endoscopic *** frequency of post-ERCP pancreatitis in PD stent and non-stent groups was 1.7%(1/60) and 13.3%(8/60),*** severity of pancreatitis was mild in all *** frequency of post-ERCP pancreatitis in the stent group was significantly lower than in the non-stent group(P = 0.032,Fisher's exact test).The rate of hyperamylasemia were 30%(18/60) and 38.3%(23 of 60) in the stent and non-stent groups,respectively(P = 0.05,χ2 test).The placement of a PD stent was successful in all 60 *** rate of spontaneous dislodgement by the third day was 96.7%(58/60),and the median(range) time to dislodgement was 2.1(2-

关键词： Endoscopic retrograde cholangiopancreatography Pancreatitis Postoperative complications Prophylaxis Stents

Causal role of Helicobacter pylori infection and eradication therapy in gastric carcinogenesis

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World Journal of Gastroenterology 2006年第1期12卷 10-16页

作者： Masanori ito Shinji Tanaka Tomoari Kamada Ken Haruma Kazuaki Chayama Department of Medicine and Molecular Science Hiroshima UniversityHiroshimaJapan Department of Endoscopy Hiroshima University HospitalHiroshimaJapan Gastroenterology Unit Department of Internal MedicineKawasaki Medical SchoolKurashikiJapan

Many epidemiological reports indicate that Helicobacter pylori （H pylori） infection plays an important role in gastric carcinogenesis. Several genetic and epigenetic alterations contribute to the initiation, promotion, and progression of the cancer cells in a multi-step manner. H pylori is known to induce chronic inflammation in the gastric mucosa. Its products, including superoxides, participate in the DNA damage followed by initiation, and the inflammation-derived cytokines and growth factors contribute to the promotion of gastric carcinogenesis. By eradicating H pylori, gastric inflammation can be cured; the therapy diminishes the levels not only of inflammatory cell infiltration, but also atrophy/ intestinal metaplasia in part. A randomized controlled trial revealed that the eradication therapy diminished the gastric cancer prevalence in cases without precancerous conditions. In addition, recent epidemiological studies from Japanese groups demonstrated that the development of gastric cancer, especially of the intestinal type, was decreased by successful eradication therapy, although these were designed in a non- randomized manner. However, it should be mentioned that endoscopic detection is the only way to evaluate the degree of gastric carcinogenesis. We have reported that the endoscopic and histological morphologies could be modified by eradication therapy and it might contribute to the prevalence of gastric cancer development. Considering the biological nature of cancer cell proliferation, it is considered that a sufficiently long-term follow-up would be essential to discuss the anticancer effect of eradication therapy.

关键词： H pylori Eradication Gastritis Gastric neoplasm, Endoscopy

Design of ionic liquids as liquid desiccant for an air conditioning system

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Green Energy & Environment 2019年第2期4卷 139-145页

作者： Haruki Watanabe Takuro Komura Ryo Matsumoto Kenta ito Hiroshi Nakayama Toshiki Nokami Toshiyuki itoh Department of Chemistry and Biotechnology Graduate School of Engineering Tottori University Chubu Electric Power Company Inc. Research and Development Division Energy Application Research and Development Center Center for Research on Green Sustainable Chemistry Tottori University

Suitable control of the humidity can contribute to electric energy savings. However, the present dehumidification system has many weak points. The liquid desiccant air-conditioning system has recently gained growing interest from the stand point of reducing energy consumption during dehumidification. In order to find the appropriate ionic liquids(ILs) as a desiccant for the liquid desiccant air-conditioner system, we conducted a systematic evaluation of the humidification capability of 16 types of ILs. Among the tested ILs, tributyl(methyl)phosphonium dimethyl phosphate([P4441][DMPO_4]) exhibited the best dehumidification capacity and had a less corrosive effect on four types of metals as possible piping materials. It should be noted that this [P_(4441)][DMPO_4] has a very stable nature and produced no odor while conducting the experiment and storing for over 1 year at room temperature under ambient conditions. Furthermore, it was revealed that a 77%(w/w) aqueous solution of [P4441][DMPO_4] worked as an efficient desiccant liquid for the liquid desiccant air-conditioner system.

关键词： Dehumidification Liquid desiccant Ionic liquids Air-conditioner system Phosphonium ILs

DAMAGE ANALYSIS BY BOUNDARY ELEMENT METHOD

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Acta Mechanica Solida Sinica 1994年第3期7卷 245-255页

作者： Z.Z.Cen G.Swoboda F.ito Tsinghua University BeijingChina Innsbruck University InnsbruckAustria

The response of cracked bodies subjected to loading was investigated by the boundary element method in this paper. The two-law elastic-cohesive-softening model was used for crack propagation analysis. The interface conditions for uncracked, craze, open crack, adhesive crack and slid crack parts were discussed and the corresponding incremental iteration algorithm was given. A simplified damage propagation model was presented. The technique has been applied to some specific examples which give the evidence that the method is satisfactory and efficient.

关键词： Algorithms Boundary element method Crack propagation Cracks Dynamic response Elasticity Fracture mechanics Interfaces (materials) Iterative methods Loads (forces) Mathematical models

Action Mechanisms of Complementary and Alternative Medicine Therapies for Rheumatoid Arthritis

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Chinese Journal of Integrative Medicine 2011年第10期17卷 723-730页

作者： Imada Keisuke 边宝林李向东 Sato Takashi ito akira Department of Biochemistry and Molecular Biology School of PharmacyTokyo University of Pharmacy and Life Sciences1432-1 HorinouchiHachiojiTokyo(192-0392)Japan China Academy of Chinese Medical Sciences

Rheumatoid arthritis （RA） is characterized as a chronic inflammatory disease in joints and concomitant destruction of cartilage and bone. Cartilage extracellular matrix components, such as type Ⅱ collagen and aggrecan are enzymatically degraded by matrix metalloproteinases （MMPs） and aggrecanases in RA. Currently, treatments targeting cytokines, including anti-tumor necrosis factor （TNF） α antibodies, soluble TNF receptor, anti-interleukin （IL）-6 receptor antibody, and IL-1 receptor antagonist, are widely used for treating RA in addition to anti- inflammatory agents and disease-modifying antirheumatic drugs （DMARDs）, such as methotrexate, but these treatments have some problems, especially in terms of cost and the increased susceptibility of patients to infection in addition to the existence of Iow-responders to these treatments. Therefore, therapeutics that can be safely used for an extended period of time would be preferable. Complementary and alternativemedicines including traditional Chinese medicines （TCM） have been used for the arthritic diseases through the ages. Recently, there are many reports concerning the anti-arthritic action mechanisms of TCM-based herbal formulas and crude herbal extracts or isolated ingredients. These natural herbal medicines are thought to moderately improve RA, but they exert various actions for the treatment of RA. In this review, the current status of the mechanism exploration of natural compounds and TCM-based herbal formulas are summarized, focusing on the protection of cartilage destruction in arthritic diseases including RA and osteoarthritis.

关键词： rheumatoid arthritis extracellular matrix aggrecanase matrix metalloproteinase complementary and alternative medicine

A nucleotide substitution at the 5′ splice site of intron 1 of rice HEADING DATE 1(HD1) gene homolog in foxtail millet, broadly found in landraces from Europe and Asia

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The Crop Journal 2015年第6期3卷 481-488页

作者： Kenji Fukunaga Naoko Izuka Takehiro Hachiken Satoshi Mizuguchi Hidemi ito Katsuyuki Ichitani Faculty of Life and Environmental Sciences Prefectural University of Hiroshima Faculty of Agriculture Kagoshima University

We investigated genetic variation of a rice HEADING DATE 1(HD1) homolog in foxtail ***, we searched for a rice HD1 homolog in a foxtail millet genome sequence and designed primers to amplify the entire coding sequence of the gene. We compared full HD1 gene sequences of 11 accessions(including Yugu 1, a Chinese cultivar used for genome sequencing) from various regions in Europe and Asia, found a nucleotide substitution at a putative splice site of intron 1, and designated the accessions with the nucleotide substitution as carrying a splicing variant. We verified by RT-PCR that this single nucleotide substitution causes aberrant splicing of intron 1. We investigated the geographical distribution of the splicing variant in 480 accessions of foxtail millet from various regions of Europe and Asia and part of Africa by d CAPS and found that the splicing variant is broadly distributed in Europe and Asia. Differences of heading times between accessions with wild type allele of the HD1 gene and those with the splicing variant allele were unclear. We also investigated variation in 13 accessions of ssp. viridis, the wild ancestor, and the results suggested that the wild type is predominant in the wild ancestor.

关键词： Foxtail millet Geographical distribution HD1(HEADING DATE 1) homolog Setaria italica Splice site

Investigation of transient and heterogeneous micro-climate around a human body in an enclosed personalized work environment

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能源与人工环境(英文) 2020年第4期1卷 423-431页

作者： Chong Wang Sung-Jun Yoo Shin-ichi Tanabe Kazuhide ito Interdisciplinary Graduate School of Engineering Sciences Kyushu UniversityJapan Faculty of Engineering Sciences Kyushu UniversityJapan Faculty of Science and Engineering Waseda UniversityJapan

Heterogeneous distribution of indoor environmental quality is known to have a great impact on human health,comfort,and productivity.A personalized work environment,that creates a localized and independent environ-ment with capsules or partitions,is being developed worldwide to provide workers with a space that enables undisturbed concentration on studying and ***,the minimized interior space of a personalized work environment can immediately cause adverse health impacts for occupant if the air quality and thermal en-vironment in the personalized work environment is not controlled ***,constant breathing can sharply increase the CO 2 concentrations in an interior space with an insufficient ventilation *** order to design a healthy and comfortable indoor environment,especially in a personalized work environment,it is important to predict precisely and comprehensively the transient and heterogeneous structure of the indoor envi-ronment formed around a human *** this background,we have developed an in silico human model that integrates a computational human model(virtual manikin combined with thermoregulation models)and respi-ratory model(virtual airway)for estimating indoor environmental quality,targeting the microclimate around a human body and breathing zone with high *** this study,we report the applicability of a comprehensive in silico human model to estimate the environ-mental quality in a personalized work environment.A coupled analysis of heat and contaminant transfer with computational fluid dynamics was conducted targeting the space around the in silico human model installed in a virtual personalized work *** informative data including human thermal comfort and breathing air quality were obtained,potentially forming the basis for the development of a digital twin of the personalized work environment and contributing to the design of a healthy,comfortable,and productive personalized work environme

关键词： Microclimate Indoor environment Digital twin Personalized work environment Computational fluid dynamics in silico human model