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Essential cellular modules for the proliferation of the primitive cell

Geoscience Frontiers 2018年第4期9卷 1155-1161页

作者： Koichi Higashi Yoshikazu Kawai Tomoya Baba Ken Kurokawa Taku Oshima Genome Evolution Laboratory National Institute of Genetics Centre for Bacterial Cell Biology Institute for Cell and Molecular BiosciencesMedical SchoolNewcastle University Advanced Genomics Center National Institute of Genetics Earth-Life Science Institute Tokyo Institute of Technology Graduate School of Biological Sciences Nara Institute of Science and Technology

Bacteria appeared early in the evolution of cellular life on planet Earth, and therefore the universally essential genes or biological pathways found across bacterial domains may represent fundamental genetic or cellular systems used in early life. The essential genes and the minimal gene set required to support bacterial life have recently been experimentally and computationally identified. It is, however,still hard to estimate the ancient genes present in primitive cells compared to the essential genes in contemporary bacteria, because we do not know how ancestral primitive cells lived and proliferated, and therefore cannot directly evaluate the essentiality of the genes in ancestral primitive cells. The cell wall is normally essential for bacterial proliferation and cellular division of walled bacterial cells is normally highly controlled by the essential FtsZ cell division machinery. But, bacteria are capable of reverting to their cell wall deficient ancestral form, called the ＂L-form＂. Unlike ＂normal＂ cells, L-forms divide by a simple physical mechanism based on the effects of membrane dynamics, suggesting a mode of primitive proliferation before the appearance of the cell wall. In this review, we summarize the experimental and computational investigations of minimal gene sets and discuss the minimal cellular modules required to support the proliferation of primitive cells, based on L-form proliferation.

关键词： L-form Essential genes Minimal gene set KEGG module Bacteria

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Nine requirements for the origin of Earth’s life:Not at the hydrothermal vent, but in a nuclear geyser system

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Geoscience Frontiers 2019年第4期10卷 1337-1357页

作者： Shigenori Maruyama Ken Kurokawa Toshikazu Ebisuzaki Yusuke Sawaki Konomi Suda M. Santosh Earth-Life Science Institute Tokyo Institute of Technology2-12-1 O-okayamaMeguro-kuTokyo 152-8551Japan Kochi University Kochi 780-8520Japan Novosibirsk State University Pirogova 1630090Russia Genome Evolution Laboratory National Institute of Genetics1111 YataMishimaShizuoka 411-8540Japan RIken 2-1 HirosawaWakoSaitama351-0198Japan Department of Earth and Planetary Sciences Graduate School of Science and EngineeringTokyo Institute of Technology2-12-1 OokayamaMeguro-kuTokyo 152-8550Japan Department of Earth Science and Astronomy Graduate School of Arts and Sciences The University of Tokyo3-8-1 KomabaMeguro-kuTokyo 153-8902Japan Geomicrobiology Research Group Institute for Geo-Resources and EnvironmentNational Institute of Advanced Industrial Science and Technology (AIST)Central 71-1-1 HigashiTsukubaIbaraki 305-8567Japan Centre for Tectonics Resources and ExplorationDepartment of Earth SciencesUniversity of AdelaideSA 5005Australia School of Earth Sciences and Resources China University of Geosciences (Beijing)29 Xueyuan RoadBeijing 100083China

The origin of life on Earth remains enigmatic with diverse models and debates.Here we discuss essential requirements for the first emergence of life on our planet and propose the following nine requirements:(1)an energy source(ionizing radiation and thermal energy);(2)a supply of nutrients(P.K.REE.etc.);(3)a supply of life-constituting major elements;(4)a high concentration of reduced gases such as CH4,HCN and NH3;(5)dry-wet cycles to create membranes and polymerize RNA;(6)a non-toxic aqueous environment;(7)Na-poor water;(8)highly diversified environments,and(9)cyclic conditions,such as dayto-night,hot-to-cold etc.Based on these nine requirements,we evaluate previously proposed locations for the origin of Earth’s life,including:(1)Darwin’s"warm little pond",leading to a"prebiotic soup"for life;(2)panspermia or Neo-panspermia(succession model of panspermia);(3)transportation from/through Mars;(4)a deepsea hydrothermal system;(5)an on-land subduct ion-zone hot spring,and(6)a geyser systems driven by a natural nuclear reactor.We conclude that location(6)is the most ideal candidate for the o rigin point for Earth’s life because of its efficiency in continuously supplying both the energy and the necessary materials for life,thereby maintaining the essential"cradle"for its initial development.We also emphasize that falsifiable working hypothesis provides an important tool to evaluate one of the biggest mysteries of the universe-the origin of life.

关键词： Origin of Earth's life Nuclear geyser system Emergence and evolution of life Falsifiability

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Texture and color enhancement imaging in magnifying endoscopic evaluation of colorectal adenomas

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World Journal of Gastrointestinal Endoscopy 2022年第2期14卷 96-105页

作者： Osamu Toyoshima Toshihiro Nishizawa Shuntaro Yoshida Tomoharu Yamada Nariaki Odawara Tatsuya Matsuno Miho Obata Ken Kurokawa Chie Uekura Mitsuhiro Fujishiro Gastroenterology Toyoshima Endoscopy ClinicTokyo 157-0066Japan Department of Gastroenterology and Hepatology International University of Health and WelfareNarita HospitalNarita 286-8520ChibaJapan Department of Gastroenterology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan

BACKGROUND Olympus Corporation has developed texture and color enhancement imaging(TXI)as a novel image-enhancing endoscopic technique.AIM To investigate the effectiveness of TXI in identifying colorectal adenomas using magnifying observation.METHODS Colorectal adenomas were observed by magnified endoscopy using white light imaging(WLI),TXI,narrow band imaging(NBI),and chromoendoscopy(CE).This study adopted mode 1 of TXI.Adenomas were confirmed by histological examination.TXI visibility was compared with the visibility of WLI,NBI,and CE for tumor margin,and vessel and surface patterns of the Japan NBI expert team(JNET)classification.Three expert endoscopists and three non-expert endoscopists evaluated the visibility scores,which were classified as 1,2,3,and 4.RESULTS Sixty-one consecutive adenomas were evaluated.The visibility score for tumor margin of TXI(3.47±0.79)was significantly higher than that of WLI(2.86±1.02,P<0.001),but lower than that of NBI(3.76±0.52,P<0.001),regardless of the endoscopist’s expertise.TXI(3.05±0.79)had a higher visibility score for the vessel pattern of JNET classification than WLI(2.17±0.90,P<0.001)and CE(2.47±0.87,P<0.001),but lower visibility score than NBI(3.79±0.47,P<0.001),regardless of the experience of endoscopists.For the visibility score for the surface pattern of JNET classification,TXI(2.89±0.85)was superior to WLI(1.95±0.79,P<0.01)and CE(2.75±0.90,P=0.002),but inferior to NBI(3.67±0.55,P<0.001).CONCLUSION TXI provided higher visibility than WLI,lower than NBI,and comparable to or higher than CE in the magnified observation of colorectal adenomas.

关键词： Texture and color enhancement imaging Adenoma Colonoscopy Narrow band imaging Japan NBI Expert Team Olympus

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Anticancer effect of linalool via cancer-specific hydroxyl radical generation in human colon cancer

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World Journal of Gastroenterology 2016年第44期22卷 9765-9774页

作者： kenichi Iwasaki Yun-Wen Zheng Soichiro Murata Hiromu Ito ken Nakayama Tomohiro kurokawa Naoki Sano Takeshi Nowatari Myra O Villareal Yumiko N Nagano Hiroko Isoda Hirofumi Matsui Nobuhiro Ohkohchi Department of Surgery and Organ Transplantation Faculty of Medicine University of Tsukuba Regenerative Medicine Research Center Jiangsu University Hospital Department of Regenerative Medicine Graduate School of Medicine Yokohama City University Department of Gastroenterology Faculty of Medicine University of Tsukuba Faculty of Life and Environmental Sciences Alliance of Research on North Africa University of Tsukuba

AIM To investigate the anticancer mechanisms of the monoterpenoid alcohol linalool in human colon cancer cells.METHODS The cytotoxic effect of linalool on the human colon cancer cell lines and a human fibroblast cell line was examined using the WST-8 assay. The apoptosisinducing effect of linalool was measured using the terminal deoxynucleotidyl transferase d UTP nickend labeling assay and flow cytometry with Annexin V. Oxidative stress was investigated by staining for diphenyl-1-pyrenylphosphine, which is a cellular lipid peroxidation marker, and electron spin resonance spectroscopy. Sixteen SCID mice xenografted with human cancer cells were randomized into 3 groups for in vivo analysis: control and low-dose and high-dose linalool groups. The control group was administered tap water orally every 3 d. The linalool treatment groups were administered 100 or 200 μg/kg linalool solution orally for the same period. All mice were sacrificed under anesthesia 21 d after tumor inoculation, and tumors and organs were collected for immunohistochemistry using an anti-4-hydroxynonenal antibody. Tumor weights were measured and compared between groups. RESULTS Linalool induced apoptosis of cancer cells in vitro, following the cancer-specific induction of oxidative stress, which was measured based on spontaneous hydroxyl radical production and delayed lipid peroxidation. Mice in the high-dose linalool group exhibited a 55% reduction in mean xenograft tumor weight compared with mice in the control group(P < 0.05). In addition, tumor-specific lipid peroxidation was observed in the in vivo model.CONCLUSION Linalool exhibited an anticancer effect via cancerspecific oxidative stress, and this agent has potential for application in colon cancer therapy.

关键词： Colorectal cancer Linalool Oxidative stress Electron spin resonance Lipid peroxidation

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Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virusinfected liver

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World Journal of Gastroenterology 2015年第11期21卷 3291-3299页

作者： Motoyuki Kohjima Tsuyoshi Yoshimoto Munechika Enjoji Nobuyoshi Fukushima Kunitaka Fukuizumi Tsukasa Nakamura Miho kurokawa Nao Fujimori Yusuke Sasaki Yasushi Shimonaka Yusuke Murata Susumu Koyama ken Kawabe Kazuhiro Haraguchi Yorinobu Sumida Naohiko Harada Masaki Kato Kazuhiro Kotoh Makoto Nakamuta Department of Gastroenterology and Clinical Research Center National Hospital Organization Kyushu Medical Center Health Care Center Fukuoka University Product Research Department Chugai Pharmaceutical Co.Ltd. Department of Medicine and Bioregulatory Science Kyushu University

AIM:To investigate the relationship between the ironmetabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C patients.METHODS:The hepatic expression profile of ironmetabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated.A hundred patients with chronic hepatitis C(genotype1b,n = 50; genotype 2,n = 50) were enrolled and retrospectively analyzed.Liver biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolismrelated genes and protein expression(Western blotting analysis) for ferroportin.As a control,normal liver tissue was obtained from 18 living donors of liver transplantation.Serum hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass spectrometry.RESULTS:Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus(HCV)is reported to induce iron accumulation in hepatocytes in vivo.Conversely,iron administration suppresses HCV replication in vitro.Therefore,the association between HCV infection and iron metabolism remains unclear.Compared with controls,patients had significantly higher gene expression for transferrin,iron-regulatoryproteins 1 and 2,divalent metal transporter 1,and ferroportin,but similar for transferrin receptors 1 and2,and hepcidin.When the expression profiles were compared between sustained virological response(SVR)and non-SVR patients,the former showed significantly lower transcription and protein expression of hepcidin and ferroportin.Expression of hepcidin-regulating genes,BMPR1,BMPR2,and hemojuvelin,was significantly increased,whereas BMP2 was decreased in HCV-infected liver.BMPR2 and hemojuvelin expression was significantly lower in the SVR than non-SVR group.HCV infection affects the expression of iron-metabolism-related genes,leading to iron accumulation in hepatocytes.CONCLUSION:Decreased expression of hepcidin and ferroportin in SV

关键词： Chronic hepatitis C Iron-metabolism Hepcidin Ferro

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Long-lasting responses after discontinuation of nivolumab treatment for reasons other than tumor progression in patients with previously treated,advanced non-small cell lung cancer

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Cancer Communications 2019年第1期39卷 665-669页

作者： Hideharu Kimura Tomoyuki Araya Taro Yoneda Hiroki Shirasaki Koji kurokawa Tamami Sakai Hayato Koba Yuichi Tambo Shingo Nishikawa Takashi Sone Kazuo Kasahara Respiratory Medicine Kanazawa University HospitalTakara-machi 13-1KanazawaIshikawa 920-8641Japan Respiratory Medicine National Hospital Organization Kanazawa Medical CenterKanazawaIshikawa 920-8650Japan Respiratory Medicine Komatsu Municipal HospitalKomatsuIshikawa 923-8560Japan Respiratory Medicine Fukui-ken Saiseikai HospitalFukuiFukui 918-8503Japan Respiratory Medicine Ishikawa Prefectural Central HospitalKanazawaIshikawa 920-8530Japan Internal Medicine Keiju Medical CenterNanaoIshikawa 926-8605Japan Regional Respiratory Symptomatology Kanazawa University Graduate School of Medical ScienceKanazawaIshikawa 920-8641Japan

Dear Editor,Nivolumab,an inhibitor of programmed cell death 1(PD-1),is an immune checkpoint inhibitor(ICI)that enhances T cell functions by preventing negative regulation of cancer immunity,and it has shown clinically significant efficacy and tolerability in various types of cancer.Based on the results of randomized phase III trials comparing nivolumab with docetaxel[1,2],nivolumab is now used in clinical practice for patients with previously treated advanced non-small cell lung cancer(NSCLC).Fur-thermore,the most recent Japan Lung Cancer Society guidelines include nivolumab monotherapy in the sys-temic treatment strategy for previously treated,locally advanced or metastatic NSCLC[3].However,ICIs induce characteristic immune-related adverse events(irAEs),which are not seen with conventional cytotoxic agents or molecular targeted agents.IrAEs can occur in any organ system,most typically the skin,lung,and gastrointesti-nal,hepatic,and endocrine systems.

关键词： nivolumab patients lung

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