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Smad3 phospho-isoform signaling in hepatitis C virus-related chronic liver diseases

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World Journal of Gastroenterology 2014年第35期20卷 12381-12390页

作者： Takashi yamaguchi Katsunori Yoshida Miki Murata Koichi Matsuzaki Department of Gastroenterology and Hepatology Kansai Medical University

The risk of hepatocellular carcinoma (HCC) development increases as hepatitis virus C (HCV)-related liver diseases progress, especially in patients with active inflammation. Insight into hepatic carcinogenesis have emerged from recent detailed analyses of transforming growth factor-β and c-Jun-N-terminal kinase signaling processes directed by multiple phosphorylated (phospho)-isoforms of a Smad3 mediator. In the course of HCV-related chronic liver diseases, chronic inflammation and host genetic/epigenetic alterations additively shift the hepatocytic Smad3 phospho-isoform signaling from tumor suppression to carcinogenesis, increasing the risk of HCC. Chronic inflammation represents an early carcinogenic step that provides a nonmutagenic tumor-promoting stimulus. After undergoing successful antiviral therapy, patients with chronic hepatitis C could experience a lower risk of HCC as Smad3 phospho-isoform signaling reverses from potential carcinogenesis to tumor suppression. Even after HCV clearance, however, patients with cirrhosis could still develop HCC because of sustained, intense carcinogenic Smad3 phospho-isoform signaling that is possibly caused by genetic or epigenetic alterations. Smad3 phospho-isoforms should assist with evaluating the effectiveness of interventions aimed at reducing human HCC.

关键词： Chronic inflammation c-Jun N-terminal kinase Hepatitis C virus Hepatocellular carcinoma Smad3 phospho-isoform signaling Transforming growth factor β

Early gastric cancer diagnostic ability of ultrathin endoscope loaded with laser light source

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World Journal of Gastroenterology 2019年第11期25卷 1378-1386页

作者： Takuto Suzuki Yoshiyasu Kitagawa Rino Nankinzan Taketo yamaguchi Department of Endoscopy Chiba Cancer Center Department of Gastroenterology Chiba Cancer Center

BACKGROUND Conventionally, the low luminous intensity, low image resolution, and difficulty in operation have been reported with the ultrathin endoscope. However, it has markedly advanced recently. The improvement of the diagnostic ability is *** To compare the early gastric cancer diagnostic ability of an ultrathin endoscope loaded with a laser light source and that of the conventional *** The target subjects were 375 consecutive patients who underwent endoscopy at our hospital for post-endoscopic submucosal dissection follow-up of gastric cancer from January to August 2018. During endoscopy, the ultrathin endoscope was used in 140 patients(37.3%), and the conventional endoscope was used in235 patients(62.7%). Patient background was adjusted using the propensity score matching method, and gastric cancer detection ability was evaluated in the two *** The gastric cancer detection rate was 7.8% in the ultrathin endoscope group and7.0% in the conventional endoscope group, and the mean intragastric observation time was 4.1 ± 1.7 min in the ultrathin endoscope group and 4.1 ± 1.9 min in the conventional endoscope group, showing no significant differences between the groups. Moreover, the biopsy implementation rate was 31.8% in the ultrathin endoscope group and 41.1% in the conventional endoscope group, and the biopsy prediction rate was 17.9% and 13.2%, respectively, showing no significant differences between the *** The gastric cancer diagnostic ability of the ultrathin endoscope loaded with a laser light source was comparable to that of the conventional endoscope. The observation time was also comparable. Thus, endoscopy using the ultrathin endoscope loaded with the laser light source would be the first option in screening examinations of gastric cancer due to its low invasion.

关键词： Conventional endoscope Gastric cancer Laser light source Screening Ultrathin endoscope

Excited-state conformation capture by supramolecular chains towards triplet-involved organic emitters

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Chinese Chemical Letters 2021年第5期32卷 1669-1674页

作者： Hao Liu Naoki Ando Shigehiro yamaguchi Pance Naumov Hongyu Zhang State Key Laboratory of Supramolecular Structure and Materials College of ChemistryJilin UniversityChangchun 130012China Department of Chemistry Graduate School of Scienceand Integrated Research Consortium on Chemical Sciences(IRCCS)Nagoya UniversityFuro ChikusaNagoya 464-8602Japan Institute of Transformative Bio-Molecules(WPI-ITbM) Nagoya UniversityFuro ChikusaNagoya 464-8602Japan New York University Abu Dhabi PO Box 129188Abu DhabiUnited Arab Emirates

Nowadays,the development of trip let-involved materials becomes a hot research topic in solid-state luminescence ***,the mechanism of trip let-involved emission still remains some mysteries to ***,we proposed a new concept of excited-state confo rmation capture for the const ructio ns of different types of trip let-involved ***,excited-state conformation could be trapped by supramolecular chains in crystal and fo rm a new optimum excited-state structure which is different from that in solution or simple rigid environment,leading to bright thermally activated delayed fluorescence(TADF) *** on excited-state conformation capture methodology,next,we obtained roomtemperature phosphorescence(RTP) by introducing Br atoms for the enhancement of intersystem *** could be concluded from experime ntal results that TADF may originate from aggregate effect while RTP may derive from ***,heavy-atom free RTP and ultra RTP were achieved by eliminating aggregate *** wo rk could not only exte nd the design methodology of triplet-involved materials but also set clear evidences for the mechanism of triplet-involved emissions.

关键词： Room-temperature phosphorescence Supramolecular chains Conformation capture Organic emitters Triplet-involved emission

Arabidopsis CBL-Interacting Protein Kinases Regulate Carbon/Nitrogen-Nutrient Response by Phosphorylating Ubiquitin Liqase ATL31

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Molecular Plant 2017年第4期10卷 605-618页

作者： Shigetaka Yasuda Shoki Aoyama Yoko Hasegawa Takeo Sato Junji yamaguchi Faculty of Science and Graduate School of Life Science Hokkaido University Sapporo 060-0810 Japan

In response to the ratio of available carbon （C） and nitrogen （N） nutrients, plants regulate their metabolism, growth, and development, a process called the C/N-nutrient response. However, the molecular basis of C/N-nutrient signaling remains largely unclear. In this study, we identified three CALCINEURIN B-LIKE （CBL）-INTERACTING PROTEIN KINASES （CIPKs）, CIPK7, CIPK12, and CIPK14, as key regulators of the C/N-nutrient response during the post-germination growth in Arabidopsis. Single-knockout mutants of ClPK7, CIPK12, and CIPK14 showed hypersensitivity to high C/low N conditions, which was enhanced in their triple-knockout mutant, indicating that they play a negative role and at least partly function redun- dantly in the C/N-nutrient response. Moreover, these CIPKs were found to regulate the function of ATL31, a ubiquitin ligase involved in the C/N-nutrient response via the phosphorylation-dependent ubiquitination and proteasomal degradation of 14-3-3 proteins. CIPK7, CIPK12, and CIPK14 physically interacted with ATL31, and CIPK14, acting with CBL8, directly phosphorylated ATL31 in a Ca2＋-dependent manner. Further analyses showed that these CIPKs are required for ATL31 phosphorylation and stabilization, which medi- ates the degradation of 14-3-3 proteins in response to C/N-nutrient conditions. These findings provide new insights into C/N-nutrient signaling mediated by protein phosphorylationo

关键词： nutrient response signal transduction ubiquitin ligase protein phosphorylation Arabidopsis

Linker phosphorylation of Smad3 promotes fibro-carcinogenesis in chronic viral hepatitis of hepatocellular carcinoma

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World Journal of Gastroenterology 2014年第41期20卷 15018-15027页

作者： Miki Murata Katsunori Yoshida Takashi yamaguchi Koichi Matsuzaki Department of Gastroenterology and Hepatology Kansai Medical University

Epidemiological and clinical data point to a close association between chronic hepatitis B virus infection or chronic hepatitis C virus infection and development of hepatocellular carcinoma (HCC). HCC develops over several decades and is associated with fibrosis. This sequence suggests that persistent viral infection and chronic inflammation can synergistically induce liver fibrosis and hepatocarcinogenesis. The transforming growth factor-β (TGF-β) signaling pathway plays a pivotal role in diverse cellular processes and contributes to hepatic fibro-carcinogenesis under inflammatory microenvironments during chronic liver diseases. The biological activities of TGF-β are initiated by the binding of the ligand to TGF-β receptors, which phosphorylate Smad proteins. TGF-β type I receptor activates Smad3 to create COOH-terminally phosphorylated Smad3 (pSmad3C), while pro-inflammatory cytokine-activated kinases phosphorylates Smad3 to create the linker phosphorylated Smad3 (pSmad3L). During chronic liver disease progression, virus components, together with pro-inflammatory cytokines and somatic mutations, convert the Smad3 signal from tumor-suppressive pSmad3C to fibro-carcinogenic pSmad3L pathways, accelerating liver fibrosis and increasing the risk of HCC. The understanding of Smad3 phosphorylation profiles may provide new opportunities for effective chemoprevention and personalized therapy for patients with hepatitis virus-related HCC in the future.

关键词： Chronic viral hepatitis Transforming growth factor-β Smad3 Phosphorylation Fibro-carcinogenesis Hepatocellular carcinoma

Xanthogranulomatous cholecystitis mimicking gallbladder carcinoma with a false-positive result on fluorodeoxyglucose PET

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World Journal of Gastroenterology 2009年第29期15卷 3691-3693页

作者： Isamu Makino Takahiro yamaguchi Nariatsu Sato Toshiaki Yasui Ichiro Kita Department of Surgery Kanazawa Social Insurance Hospital Kanazawa Ishikawa 920-8610 Japan

Recently, several reports have demonstrated that fluorine-18 fluorodeoxyglucose positron emission tomography （FDG-PET） is useful in differentiating between benign and malignant lesions in the gallbladder. However, there is a limitation in the ability of FDG-PET to differentiate between inflammatory and malignant lesions. We herein present a case of xanthogranulomatous cholecystitis misdiagnosed as gallbladder carcinoma by ultrasonography and computed tomography. FDG-PET also showed increased activity. In this case, FDG-PET findings resulted in a false-positive for the diagnosis of gallbladder carcinoma.

关键词： Fluorodeoxyglucose F18 Positron-emissiontomography Xanthogranulomatous cholecystitis Gallbladder cancer

Safety and efficacy of self-expandable metallic stents in malignant small bowel obstructions

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World Journal of Gastroenterology 2016年第40期22卷 9022-9027页

作者： Akiyoshi Tsuboi Toshio Kuwai Tomoyuki Nishimura Sumio Iio Takeshi Mori Hiroki Imagawa Toshiki yamaguchi Atsushi yamaguchi Hirotaka Kouno Hiroshi Kohno Department of Gastroenterology National Hospital Organization Kure Medical Center and Chugoku Cancer Center

In this report, we present 3 cases of malignant small bowel obstruction, treated with palliative care using endoscopic self-expandable metallic stent(SEMS) placement, with the aim to identify the safety and efficacy of this procedure. Baseline patient characteristics, procedure methods, procedure time, technical and clinical success rates, complications, and patient outcomes were obtained. All 3 patients had pancreatic cancer with small bowel strictures. One patient received the SEMS using colonoscopy, while the other 2 patients received SEMS placement via double balloon endoscopy using the through-the-overtube technique. The median procedure time was 104 min. The technical and clinical success rates were 100%. Post-treatment, obstructive symptoms in all patients improved, and a low-residue diet could be tolerated. All stents remained within the patients until their deaths. The median overall survival time(stent patency time) was 76 d. SEMS placement is safe and effective as a palliative treatment for malignant small bowel obstruction.

关键词： Self-expandable metallic stents Malignant small bowel obstructions Endoscopy Case report Pancreatic cancer

Configuration of Shock Waves in Two-Dimensional Overexpanded Jets

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Journal of Thermal Science 2003年第4期12卷 294-298页

作者： Masashi Kashitani Yutaka yamaguchi Yoshiaki Miyazato Mitsuharu Masuda Kazuyasu Matsuo Department of Aerospace Engineering National Defense Academy 1-10-20 Hashirimizu Yokosuka Kanagawa 239-8686 JapanDepartment of Aerospace Engineering National Defense Academy 1-10-20 Hashirimizu Yokosuka Kanagawa 239-8686 JapanDepartment of Energy and Environmental Engineering Kyushu University 6-1 Kasuga-Kouen Kasuga Fukuoka 816-8580 JapanDepartment of Energy and Environmental Engineering Kyushu University 6-1 Kasuga-Kouen Kasuga Fukuoka 816-8580 JapanDepartment of Mechanical Systems and Environmental Engineering The University of Kitakyushu 1-1 Hibikino Wakamatsu-ku Kitakyushu Fukuoka 808-0315 Japan

An experimental and analytical study has been carried out to obtain the clear understanding of a shock wave transition associated with a steady two-dimensional overexpanded flow. Two-dimensional inviscid theory with respect to a shock wave reflection is used in the present study on the characteristic of shock waves. The results obtained from the flow analysis are compared with those obtained from flow visualizations. It is shown that in the region of regular reflection, the angle of an incident shock wave becomes lower than that calculated by two shock theory with an increment in the ratio PJPb of the nozzle exit pressure Pc to the back pressure Pb. It is indicated that the configuration of shock waves in overexpanded jets is influenced by the divergent angle at the nozzle exit. Also it is shown from the flow visualization that a series of shock waves move into the nozzle inside with a decrease in pressure ratio Pc/Pb, even if the Pc/Pb is under overexpanded conditions.

关键词：振动波超声喷管可压缩流体膨胀喷射空气动力学

Recent update on electrochemical CO_(2)reduction catalyzed by metal sulfide materials

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Materials Reports(Energy) 2023年第2期3卷 103-123,I0003页

作者： An Niza El Aisnada Masahiro Miyauchi Min Liu Akira yamaguchi Department of Materials Science and Engineering School of Materials and Chemical TechnologyTokyo Institute of Technology2-12-1 OokayamaMeguro-kuTokyo152=8552Japan Biofunctional Catalyst Research Team RIKEN Center for Sustainable Resource Science2=1 HirosawaWakoSaitama351-0198Japan Hunan Joint International Research Center for Carbon Dioxide Resource Utilization State Key Laboratory of Powder MetallurgySchool of Physical and ElectronicsCentral South UniversityChangsha410083China

Seeking and developing efficient CO_(2)reduction reaction(CO_(2)RR)electrocatalysts is a hot topic in this era of global *** material candidates for sustainable and cost-effective applications,metal sulfides have attracted attention as promising nature-inspired materials due to multiple adsorption sites which are enhanced by the covalent character of *** article summarizes the current status regarding the utilization and development of metal sulfide materials as CO_(2)RR ***,the research background and basic principles of electrochemical CO_(2)RR are ***,an overview of the main obstacles to developing efficient CO_(2)RR electrocatalysts is *** section is followed by a summary of the empirical evidence supporting the application of metal sulfides as CO_(2)RR electrocatalysts beside nature-inspired *** summary of synthesis methods of various metal sulfides is also ***,the paper also highlights the recent works on metal sulfide as efficient CO_(2)RR including the undertaking strategy on the activity enhancement,and finally,discusses the challenges and prospect of metal sulfides-based CO_(2)RR *** recent efforts,metal sulfides remain relatively unexplored as materials for CO_(2)RR electrocatalytic ***,this review aims to stimulate novel ideas and research for improved catalyst designs and functionality.

关键词： Metal sulfides Electrocatalyst Electrochemical CO_(2)reduction Bi-metal sulfides Active site Defect engineering Selectivity Faradaic efficiency