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Highlights of the 2nd International Symposium on Tribbles and Diseases: tribbles tremble in therapeutics for immunity, metabolism, fundamental cell biology and cancer

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Acta Pharmaceutica Sinica B 2019年第2期9卷 443-454页

作者： Bing Cui Patrick A. Eyers Leonard L. Dobens Nguan Soon Tan Peter D. Mace Wolfgang A. Link Endre Kiss-Toth Karen Keeshan takuro nakamura Warren S. Pear Yodit Feseha Jessica Johnston Arkatiz Carracedo Marcel Scheideler Zabran llyas Robert C. Bauer Jorge D. Erusalimsky Dominika Grzesik Juan Salamanca-Viloria Xiaoxi Lv Yishi Jin Ke Li Guillermo Velasco Shuang Shang Jose M. Lizcano Xiaowei Zhang Jichao Zhou Jiaojiao Yu Fang Hua Feng Wang Shanshan Liu Jinmei Yu Zhuowei Hu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Department of Biochemistry Institute of Integrative Biology University of Liverpool Division of Molecular Biology and Biochemistry School of Biological Sciences University of Missouri-Kansas City School of Biological Sciences Nanyang Technological University Lee Kong Chian School of Medicine Nanyang Technological University Institute of Molecular and Cell Biology KK Women's and Children Hospital Biochemistry Department School of Biomedical Sciences University of Otago Centre for Biomedical Research (CBMR) University of Algarve Campus de Gambelas Department of Biomedical Sciences and Medicine University of Algarve Algarve Biomedical Center (ABC) University of Algarve Campus de Gambelas Department of Infection Immunity and Cardiovascular Disease University of Sheffield Paul O'Gorman Leukaemia Research Centre Institute of Cancer Sciences University of Glasgow Division of Carcinogenesis The Cancer Institute Japanese Foundation for Cancer Research Department of Pathology and Laboratory Medicine Abramson Family Cancer Research Institute Perelman School of Medicine at the University of Pennsylvania Centre de Recherche en Transplantation et Immunologie (ou CRTI) Inserm Université de Nantes Nantes France Institut de Transplantation Urologie Néphrologie (ou ITUN) CIC bioGUNE CIBERONC Ikerbasque Basque Foundation for Science Biochemistry and Molecular Biology Department University of the Basque Country (UPV/EHU) Institute for Diabetes and Cancer IDC Helmholtz Center Munich Joint Heidelberg-IDC Translational Diabetes Program University Hospital Heidelberg Molecular Metabolic Control Medical Faculty Technical University Munich German Center for Diabetes Research (DZD) Division of Cardiology Department of Medicine Columbia University Irving Medical Center School of Sport and Health Sciences Cardiff Metropolitan Universit

The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2 nd International Symposium on Tribbles and Diseases held on May 7–9, 2018 in Beijing, China, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases.

关键词： Tribbles Immunology Metabolism Cell biology Kinase inhibitor Tumorigenesis Metastasis TRIB1 TRIB2 TRIB3 Pseudokinase Inflammation Atomic structure Protein quality control Ubiqutin

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Upconversion time-stretch infrared spectroscopy

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Light(Science & Applications) 2023年第3期12卷 465-474页

作者： Kazuki Hashimoto Takuma nakamura Takahiro Kageyama Venkata Ramaiah Badarla Hiroyuki Shimada Ryoich Horisaki takuro Ideguchi Institute for Photon Science and Technology The University of TokyoTokyo113-0033Japan Department of Physics The University of TokyoTokyo113-0033Japan Graduate School of Information Science and Technology The University of TokyoTokyo113-8656Japan

High-speed measurement confronts the extreme speed limit when the signal becomes comparable to the noise *** the context of broadband mid-infrared spectroscopy,state-of-the-art ultrafast Fourier-transform infrared spectrometers,in particular dual-comb spectrometers,have improved the measurement rate up to a few MSpectra s^(-1),which is limited by the signal-to-noise ***-stretch infrared spectroscopy,an emerging ultrafast frequency-swept mid-infrared spectroscopy technique,has shown a record-high rate of 80 MSpectra s^(-1) with an intrinsically higher signal-to-noise ratio than Fourier-transform spectroscopy by more than the square-root of the number of spectral ***,it can measure no more than~30 spectral elements with a low resolution of several ***,we significantly increase the measurable number of spectral elements to more than 1000 by incorporating a nonlinear upconversion *** one-to-one mapping of a broadband spectrum from the mid-infrared to the near-infrared telecommunication region enables low-loss time-stretching with a single-mode optical fiber and low-noise signal detection with a high-bandwidth *** demonstrate high-resolution mid-infrared spectroscopy of gas-phase methane molecules with a high resolution of 0.017 cm^(-1).This unprecedentedly high-speed vibrational spectroscopy technique would satisfy various unmet needs in experimental molecular science,e.g.,measuring ultrafast dynamics of rreversible phenomena,statistically analyzing a large amount of heterogeneous spectral data,or taking broadband hyperspectral images at a high frame rate.

关键词： spectroscopy noise resolution

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Monocyte-derived fibrocytes elimination had little contribution on liver fibrosis

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Hepatobiliary & Pancreatic Diseases International 2019年第4期18卷 348-353页

作者： Yoshinori Ozono Kotaro Shide Fumiyo Toyoshima Yuuka Takaishi Mai Tsuchimochi Ayako Kamiunten takuro Kameda Kenichi nakamura Tadashi Miike Kazunori Kusumotoa Hisayoshi Iwakiri Satoru Hasuikea Kenji Nagata Akira Sawaguchi Kazuya Shimoda Department of Gastroenterology and Hematology Faculty of MedicineUniversity of Miyazaki5200 KiharaKiyotakeMiyazaki 889-1601Japan Department of Anatomy Ultrastructural Cell BiologyFaculty of MedicineUniversity of Miyazaki5200 KiharaKiyotakeMiyazaki 889-1601Japan Department of Liver disease University of Miyazaki HospitalMiyazakiJapan

Background:Monocyte-derived fibrocytes play an important role in the progression of fibrosis in the skin,lungs,heart and ***,the contribution of fibrocytes to liver fibrosis is *** aim of this study was to investigate whether fibrocytes contributed to fibrosis progression in the livers of carbon tetrachloride(CCl 4)-treated ***:C57BL/6J mice were divided into 4 groups:normal control group,CCl 4-treated group,CCl 4+control liposome-treated group,and CCl 4+clodronate liposome-treated *** the elimination of systemic monocyte and monocyte-derived fibrocyte,one group was treated with clodronate liposome,and another group with control liposome as a *** 4 weeks of treatment,hepatic mononuclear cells were subjected to immunofluorescent(IF)staining and fluorescence-activated cell sorter(FACS)analysis to detect *** of collagen-positive Sirius red stained area and collagen-I mRNA expression in the liver were performed to evaluate the degree of liver fibrosis ***:In the liver of the CCl 4-treated and CCl 4+control liposome-treated groups,the number of fibrocytes,the area positive for Sirius red staining and collagen-I mRNA expression significantly increased compared with those in the normal control *** the liver of the CCl 4+clodronate liposome-treated group,few fibrocytes was observed as in the normal control group,but Sirius red staining positive area and collagen-I mRNA expression were increased and equivalent to the CCl 4-treated and CCl 4+control liposome-treated ***:Monocyte-derived fibrocytes play a minimal role in CCl 4-induced liver *** other than fibrocytes such as hepatic stellate cells play a central role in liver fibrosis.

关键词： Fibrocytes Liver fibrosis Carbon tetrachloride Clodronate Collagen-I

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Garenoxacin Prophylaxis for Febrile Neutropenia after Chemotherapy in Hematological Malignancies

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Open Journal of Internal Medicine 2016年第4期6卷 128-138页

作者： Nobuhiko nakamura Takeshi Hara Soranobu Ninomiya Yuhei Shibata takuro Matsumoto Hiroshi nakamura Junichi Kitagawa Yasuhito Nannya Masahito Shimizu Nobuo Murakami Hisashi Tsurumi Department of Hematology Gifu University Graduate School of Medicine Gifu Japan

Background: Febrile neutropenia is one of the most serious adverse events in patients with hematological malignancies and chemotherapy. The routine use of fluoroquinolone prophylaxis in patients with hematological malignancies is controversial. Therefore, we prospectively evaluated the efficacy and safety of prophylactic use of garenoxacin for febrile neutropenia. Patients and Methods: Consecutive adult patients with hematological malignancies who were at risk for chemotherapy-induced neutropenia lasting more than seven days were eligible for present study. They received oral garenoxacin (400 mg daily) from the neutrophil count decreased to less than 1000/μl and continued until the neutropenia had resolved. The primary endpoint was incidence of febrile neutropenia, and the secondary endpoints were the type and incidence of adverse events. Results: We enrolled 46 consecutive patients (median age, 59 years). The underlying diseases comprised acute myeloid leukemia (n = 17), acute lymphoblastic leukemia (n = 3), malignant lymphoma (n = 23), and multiple myeloma (n = 3). There were 23 febrile neutropenia episodes and 2 episodes of bacteremia. There were no grade 3 or 4 adverse events;however serum creatinine levels were significantly elevated after garenoxacin administration. The overall prophylactic efficacy of garenoxacin was 50%, and there were no infection-related deaths. Conclusions: Prophylactic use of garenoxacin is effective and safe in patients with hematological malignancies. (Clinical trial registration number: UMIN000004979).

关键词： Febrile Neutropenia Prophylaxis Garenoxacin Hematological Malignancies

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Endoscopic Examination for Patients with Diarrhea after Allogeneic Stem Cell Transplantation

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Open Journal of Internal Medicine 2017年第4期7卷 105-114页

作者： Junichi Kitagawa takuro Matsumoto Yuhei Shibata Nobuhiko nakamura Hiroshi nakamura Soranobu Ninomiya Yasuhito Nannya Masahito Shimizu Takeshi Hara Hiroshi Araki Hisashi Tsurumi Department of Hematology Graduate School of Medicine Gifu University Gifu Japan Department of Gastroenterology Graduate School of Medicine Gifu University Gifu Japan

Objective: Intestinal graft-versus-host disease (GVHD) represents one of the most serious complications of allogeneic stem cell transplantation (allo-SCT). Endoscopic and histological proof is required due to the number of differential diagnoses manifesting as diarrhea. We investigated the safety of endoscopic biopsies, and the role of conducting biopsies and inspections of the terminalileum. Patients: Thirty two colonoscopic examinations and 29 biopsies were performed for 19 patients after allo-SCT in our institute between October 2011 and May 2015. Results: Endoscopic examinations and biopsies were performed safely under the policy of transfusing platelets for thrombocytopenia (3/μL). For biopsied cases, the diagnostic consistency rate with endoscopic findings was 60%, with a tendency toward negative correlations with early examinations after diarrhea onset (25% for 0 - 1 days;62.5% for later) or low-grade GVHD according to Freiburg criteria (41.2% for grade 1, 66.7% for grade 2, 100% for higher). The terminal ileum was inspected with colonoscopy in 13 cases. Endoscopic diagnoses of the ileum were provided in 11 cases and histological diagnoses in 9 cases. Diagnostic consistency for diagnosis of the terminal ileum between endoscopy and histology was 77.8%. Conclusion: Because endoscopic and histopathological findings do not always match, caution is required when focusing on endoscopic findings alone, as there is a risk of misdiagnosis. Extensive inspection of the terminal ileum with biopsy appears useful to identify otherwise undetected lesions. Our data thus support invasive endoscopic examinations for gastrointestinal complications, including ileac inspection and biopsies under appropriate management.

关键词： Intestinal GVHD Endoscopic Evaluation Ileoscopy Colonoscopy

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Successful treatment of conversion chemotherapy for initially unresectable synchronous colorectal liver metastasis

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World Journal of Gastroenterology 2015年第6期21卷 1982-1988页

作者： Kenta Baba Akihiko Oshita Mohei Kohyama Satoshi Inoue Yuta Kuroo takuro Yamaguchi Hiroyuki nakamura Yoichi Sugiyama Tatsuya Tazaki Masaru Sasaki Yuji Imamura Yutaka Daimaru Hideki Ohdan Atsushi Nakamitsu Department of Surgery JA Hiroshima General Hospital Department of Gastroenterological and Transplant Surgery Applied Life Sciences Institute of Biomedical and Health Sciences Hiroshima University Department of Pathology JA Hiroshima General Hospital

A 72-year-old woman with a sigmoid colon cancer and a synchronous colorectal liver metastasis(CRLM),which involved the right hepatic vein(RHV)and the inferior vena cava(IVC),was referred to our *** metastatic lesion was diagnosed as initially unresectable because of its invasion into the confluence of the RHV and *** she had undergone laparoscopic sigmoidectomy for the original tumor,she consequently had 3 courses of modified 5-fluorouracil,leucovorin,and oxaliplatin(m FOLFOX6)plus *** tomography revealed a partial response,and the confluence of the RHV and IVC got free from cancer *** 3 additional courses of m FOLFOX6 plus cetuximab,preoperative percutaneous transhepatic portal vein embolization(PTPE)was performed to secure the future remnant liver ***,a right hemihepatectomy was *** postoperative course was *** patient was discharged from the hospital on postoperative day *** had neither local recurrence nor distant metastasis 18 mo after the last surgical *** multidisciplinary strategy,consisting of conversion chemotherapy using FOLFOX plus cetuximab and PTPE,could contribute in facilitating curative hepatic resection for initially unresectable CRLM.

关键词： Initial y unresectable Colorectal liver metastasis

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