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Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance

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World Journal of Diabetes 2017年第3期8卷 97-103页

作者： Tomoki abe Katsuya Hirasaka takeshi Nikawa Department of Nutritional Physiology Institute of Biomedical Sciences Tokushima University Graduate School Graduate School of Fisheries Science and Environmental Studies Nagasaki University

Aging and overnutrition cause obesity in rodents and humans. It is well-known that obesity causes various diseases by producing insulin resistance(IR). Macrophages infiltrate the adipose tissue(AT) of obese individuals and cause chronic low-level inflammation associated with IR. Macrophage infiltration is regulated by the chemokines that are released from hypertrophied adipocytes and the immune cells in AT. Saturated fatty acids are recognized by toll-like receptor 4(TLR4) and induce inflammatory responses in AT macrophages(ATMs). The inflammatory cytokines that are released from activated ATMs promote IR in peripheral organs, such as the liver, skeletal muscle and AT. Therefore, ATM activation is a therapeutic target for IR in obesity. The ubiquitin ligase Casitas b-lineage lymphoma-b(Cbl-b) appears to potently suppress macrophage migration and activation. Cbl-b is highly expressed in leukocytes and negatively regulates signals associated with migration and activation. Cbl-b deficiency enhances ATM accumulation and IR in aging- and diet-induced obese mice. Cbl-b inhibits migration-related signals and SFA-induced TLR4 signaling in ATMs. Thus, targeting Cbl-b may be a potential therapeutic strategy to reduce the IR induced by ATM activation. In this review, we summarize the regulatory functions of Cbl-b in ATMs.

关键词： Casitas b-lineage lymphoma-b Insulin resistance Macrophage Obesity Toll-like receptor 4

Liver-targeted hydrodynamic gene therapy: Recent advances in the technique

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World Journal of Gastroenterology 2016年第40期22卷 8862-8868页

作者： takeshi Yokoo Kenya Kamimura Hiroyuki abe Yuji Kobayashi Tsutomu Kanefuji Kohei Ogawa Ryo Goto Masafumi Oda takeshi Suda Shuji Terai Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University Institute for Research Collaboration and Promotion Niigata University

One of the major research focuses in the field of gene therapy is the development of clinically applicable, safe, and effective gene-delivery methods. Since the first case of human gene therapy was performed in 1990, a number of gene-delivery methods have been developed, evaluated for efficacy and safety, and modified for human application. To date, viral-vectormediated deliveries have shown effective therapeutic results. However, the risk of lethal immune response and carcinogenesis have been reported, and it is still controversial to be applied as a standard therapeutic option. On the other hand, delivery methods for nonviral vector systems have been developed, extensively studied, and utilized in in vivo gene-transfer studies. Compared to viral-vector mediated gene transfer, nonviral systems have less risk of biological reactions. However, the lower gene-transfer efficiency was a critical hurdle for applying them to human gene therapy. Among a number of nonviral vector systems, our studies focus on hydrodynamic gene delivery to utilize physical force to deliver naked DNA into the cells in the living animals. This method achieves a high gene-transfer level by DNA solution injections into the tail vein of rodents, especially in the liver. With the development of genome editing methods, in vivo gene-transfer therapy using this method is currently the focus in this research field. This review explains the method principle, efficiency, safety, and procedural modifications to achieve a high level of reproducibility in large-animal models.

关键词： Gene therapy liver Hydrodynamic gene delivery Non-viral image-guided

Gravity assistance enables liver stiffness measurements to detect liver fibrosis under congestive circumstances

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World Journal of Hepatology 2022年第4期14卷 778-790页

作者： takeshi Suda Ai Sugimoto Tsutomu Kanefuji Atsushi abe takeshi Yokoo Takahiro Hoshi Satoshi abe Shinichi Morita Kazuyoshi Yagi Masashi Takahashi Shuji Terai Department of Gastroenterology and Hepatology Uonuma Institute of Community MedicineNiigata University Medical and Dental HospitalMinami Uonuma 949-7302NiigataJapan Division of Thoracic and Cardiovascular Surgery Graduate School of Medical and Dental SciencesNiigata UniversityNiigata 951-8122Japan Department of Gastroenterology and Hepatology Tsubame Rosai HospitalTsubame 959-1228NiigataJapan Department of Administration Joetsu-Area General Health Care CenterJoetsu 943-0803NiigataJapan Department of Preemptive Medicine for Digestive Diseases and Healthy Active Life Niigata University School of MedicineNiigata 951-8122Japan Division of Gastroenterology and Hepatology School of Medical and Dental SciencesNiigata UniversityNiigata 951-8122Japan

BACKGROUND As survival has been prolonged owing to surgical and medical improvements,liver failure has become a prognostic determinant in patients with congestive heart *** hepatopathy,an abnormal state of the liver as a result of congestion,insidiously proceed toward end-stage liver disease without effective biomarkers evaluating pathological *** measurements of shear wave elastography cannot qualify liver fibrosis,which is a prognosticator in any type of chronic liver disease,in cases of congestion because congestion makes the liver stiff without *** hypothesized that the effects of congestion and fibrosis on liver stiffness can be dissociated by inducing architectural deformation of the liver to expose structural *** establish a strategy measuring liver stiffness as a reflection of architectural rigidity under *** Two-dimensional shear wave elastography(2dSWE)was measured in the supine(Sp)and left decubitus(Ld)positions in 298 consecutive cases as they were subjected to an ultrasound study for various liver *** of interest were placed at twelve sites,and the median and robust coefficient of variation were *** data were compared using the Mann-Whitney U or Kruskal-Wallis test followed by Dunn's post-hoc multiple *** inferior vena cava(IVC)diameters at different body positions were compared using the Wilcoxon matched pairs signed rank *** number of cases with cardiothoracic ratios greater than or not greater than 50%was compared using Fisher’s exact test.A correlation of 2dSWE between different body positions was evaluated by calculating Spearman correlation *** The IVC diameter was significantly reduced in Ld in subjects with higher 2dSWE values in Ld(LdSWE)than in Sp(SpSWE)(P=0.007,(average±SD)13.9±3.6 vs 13.1±3.4 mm)but not in those with lower LdSWE values(P=0.32,13.3±3.5 vs 13.0±3.5 mm).In 81 subjects,SpSWE was increased or decreased in

关键词： Shear wave elastography Inferior vena cava diameter Congestive hepatopathy Liver fibrosis Body positions Fibrosis-4 index

Management and associated factors of delayed perforation after gastric endoscopic submucosal dissection

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World Journal of Gastroenterology 2015年第44期21卷 12635-12643页

作者： Haruhisa Suzuki Ichiro Oda Masau Sekiguchi Seiichiro abe Satoru Nonaka Shigetaka Yoshinaga takeshi Nakajima Yutaka Saito Endoscopy Division National Cancer Center Hospital

AIM: To identify the actual clinical management and associated factors of delayed perforation after gastric endoscopic submucosal dissection(ESD).METHODS: A total of 4943 early gastric cancer(EGC) patients underwent ESD at our hospital between January 1999 and June 2012. We retrospectively assessed the actual management of delayed perforation. In addition, to determine the factors associated with delayed perforation, after excluding 123 EGC patients with perforations that occurred during the ESD procedure, we analyzed the following clinicopathological factors among the remaining 4820 EGC patients by comparing the ESD cases with delayed perforation and the ESD cases without perforation: age, sex, chronological periods, clinical indications for ESD, status of the stomach, location, gastric circumference, tumor size, invasion depth, presence/absence of ulceration, histological type, type of resection, and procedure ***: Delayed perforation occurred in 7(0.1%) cases. The median time until the occurrence of delayed perforation was 11 h(range, 6-172 h). Three(43%) of the 7 cases required emergency surgery, while four were conservatively managed without surgical intervention. Among the 4 cases with conservative management, 2 were successfully managed endoscopically using the endoloop-endoclip technique. The median hospital stay was 18 d(range, 15-45 d). There were no delayed perforation-related deaths. Based on a multivariate analysis, gastric tube cases(OR = 11.0; 95%CI: 1.7-73.3; P = 0.013) were significantly associated with delayed ***: Endoscopists must be aware of not only the identified factors associated with delayed perforation, but also how to treat this complicationeffectively and promptly.

关键词： Early gastric cancer Endoscopic submucosal dissect

Rational arrangement of measuring shear wave speed in the liver

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World Journal of Gastroenterology 2019年第20期25卷 2503-2513页

作者： takeshi Yokoo Tsutomu Kanefuji takeshi Suda Itsuo Nagayama Takahiro Hoshi Satoshi abe Shinichi Morita Hiroteru Kamimura Kenya Kamimura Atsunori Tsuchiya Masaaki Takamura Kazuyoshi Yagi Shuji Terai Department of Preemptive Medicine for Digestive Diseases and Healthy Active Life Niigata University School of MedicineNiigataNiigata 951-8122Japan Division of Gastroenterology and Hepatology Niigata Tokamachi HospitalTokamachiNiigata 948-0065Japan Department of Gastroenterology and Hepatology Uonuma Institute of Community MedicineNiigata University Medical and Dental HospitalMinami UonumaNiigata 949-7302Japan Division of Gastroenterology and Hepatology Graduate School of Medical and Dental SciencesNiigata UniversityNiigata 951-8122Japan

BACKGROUND Shear wave speed has been widely applied to quantify a degree of liver fibrosis. However, there is no standardized procedure, which makes it difficult to utilize the speed universally. AIM To provide procedural standardization of shear wave speed measurement. METHODS Point shear wave elastography (pSWE) was measured in 781 patients, and twodimensional shear wave elastography (2dSWE) was measured on the same day in 18 cases. Regions-of-interest were placed at 12 sites, and the median and robust coefficient-of-variation (CVR) were calculated. A residual sum-of-square (Σdi2) was computed for bootstrap values of 1000 iterations in 18 cases with each assumption of 1 to 12 measurements. The proportion of the Σdi2 (%Σdi2) was calculated as the ratio of Σdi2 to pSWE after converting it based on the correlation between pSWE and 2dSWE. RESULTS The CVR showed a significantly broader distribution in the left lobe (P < 0.0001),and the smallest CVR in the right anterior segment that covered 95% cases was 40.4%. pSWE was significantly higher in the left lobe than in the right lobe (1.63 ± 0.78 m/s vs 1.61 ± 0.78 m/s, P = 0.0004), and the difference between the lobes became further discrete when the subjects were limited to the cases with a CVR less than 40.4% in any segment (1.76 ± 0.80 m/s vs 1.70 ± 0.82 m/s, P < 0.0001). The highest values of the CVR in every 0.1 m/s interval were plotted in convex upward along pSWE and peaked at 1.93 m/s. pSWE and 2dSWE were significantly correlated (P < 0.0001, r = 0.95). In 216000 resamples from 18 cases, the %Σdi2 of 12 sites was 8.0% and gradually increased as the acquisition sites decreased to reach a significant difference with a %Σdi2 of 7 sites (P = 0.027). CONCLUSION These data suggest that shear wave speed should be measured at 8 or more sites of spreading in both lobes.

关键词： Liver stiffness Ultrasound Shear wave elastography Acoustic radiation force impulse Heterogeneity

Endoscopic submucosal dissection for colorectal neoplasms:A review

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World Journal of Gastroenterology 2014年第43期20卷 16153-16158页

作者： Taku Sakamoto Genki Mori Masayoshi Yamada Yuzuru Kinjo Eriko So Seiichiro abe Yosuke Otake takeshi Nakajima Takahisa Matsuda Yutaka Saito Endoscopy Division National Cancer Center Hospital

The introduction of colorectal endoscopic submucosal dissection(ESD)has expanded the application of endoscopic treatment,which can be used for lesions with a low metastatic potential regardless of their *** has the advantage of achieving en bloc resection with a lower local recurrence rate compared with that of piecemeal endoscopic mucosal ***,in the past,surgery was indicated in patients with large lesions spreading to almost the entire circumference of the rectum,regardless of the depth of invasion,as endoscopic resection of these lesions was technically ***,a prime benefit of ESD is significant improvement in the quality of life for patients who have large rectal *** the other hand,ESD is not as widely applied in the treatment of colorectal neoplasms as it is in gastric cancers owing to the associated technical difficulty,longer procedural duration,and increased risk of *** diversify the available endoscopic treatment strategies for superficial colorectal neoplasms,endoscopists performing ESD need torecognize its indications,the technical issues involved in its application,and the associated *** review outlines the methods and type of devices used for colorectal ESD,and the training required by endoscopists to perform this procedure.

关键词： Colorectum Endoscopic submucosal dissection Short-term outcomes Training indication for endoscopic treatment

Tracing founder haplotypes of Japanese apple varieties: application in genomic prediction and genome-wide association study

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Horticulture Research 2021年第1期8卷 614-627页

作者： Mai FMinamikawa Miyuki Kunihisa Koji Noshita Shigeki Moriya Kazuyuki abe takeshi Hayashi Yuichi Katayose Toshimi Matsumoto Chikako Nishitani Shingo Terakami Toshiya Yamamoto Hiroyoshi Iwata Laboratory of Biometry and Bioinformatics Department of Agricultural and Environmental BiologyGraduate School of Agricultural and Life SciencesThe University of Tokyo1-1-1 YayoiBunkyoTokyo 113-8657Japan Institute of Fruit Tree and Tea Science National Agriculture and Food Research Organization(NARO)2-1 FujimotoTsukubaIbaraki 305-8605Japan Division of Apple Research Institute of Fruit Tree and Tea ScienceNARO92-24 Shimokuriyagawa NabeyashikiMoriokaIwate 020-0123Japan Institute of Crop Science NARO2-1-2 KannondaiTsukubaIbaraki 305-8518Japan Institute of Agrobiological Sciences NARO1-2 OwashiTsukubaIbaraki 305-8634Japan

Haplotypes provide useful information for genomics-based approaches,genomic prediction,and genome-wide association *** a small number of superior founders have contributed largely to the breeding history of fruit trees,the information of founder haplotypes may be relevant for performing the genomics-based approaches in these *** this study,we proposed a method to estimate 14 haplotypes from 7 founders and automatically trace the haplotypes forward to apple parental(185 varieties)and breeding(659 F 1 individuals from 16 full-sib families)populations based on 11,786 single-nucleotide polymorphisms,by combining multiple ***,92%of the single-nucleotide polymorphisms information in the parental and breeding populations was characterized by the 14 founder *** use of founder haplotype information improved the accuracy of genomic prediction in 7 traits and the resolution of genome-wide association study in 13 out of 27 fruit quality traits analyzed in this *** also visualized the significant propagation of the founder haplotype with the largest genetic effect in genome-wide association study over the pedigree tree of the parental *** results suggest that the information of founder haplotypes can be useful for not only genetic improvement of fruit quality traits in apples but also for understanding the selection history of founder haplotypes in the breeding program of Japanese apple varieties.

关键词： breeding varieties prediction

Prognostic factors in heart failure patients with cardiac cachexia

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Journal of Geriatric Cardiology 2020年第1期17卷 26-34页

作者： Yu Sato Akiomi Yoshihisa Yusuke Kimishima Tetsuro Yokokawa Satoshi abe takeshi Shimizu Tomofumi Misaka Shinya Yamada Takamasa Sato Takashi Kaneshiro Masayoshi Oikawa Atsushi Kobayashi Takayoshi Yamaki Hiroyuki Kunii Yasuchika Takeishi Department of Cardiovascular Medicine Fukushima Medical UniversityFukushimaJapan Department of Advanced Cardiac Therapeutics Fukushima Medical UniversityFukushimaJapan

Objective To clarify whether cardiac cachexia(CC)alters the prognostic impact of other general risk factors in patients with heart failure(HF).Methods This was an observational *** was defined as the combination of a body mass index of5 mg/L;hemoglobin<12 g/dL;and/or albumin<3.2 g/d *** divided 1608 hospitalized HF patients into a CC group(n=176,10.9%)and a non-CC group(n=1432,89.1%).The primary endpoints were cardiac event and all-cause *** The presence of CC showed significant interactions with other risk factors including cancer,estimated glomerular filtration rate(eGFR),and sodium in predicting these *** Cox proportional analysis revealed that use of a blockers[hazard ratio(HR)=1.900,95%confidence interval(CI):1.045–3.455,P=0.035]and eGFR(HR=0.989,95%CI:0.980–0.998,P=0.018)were independent predictors of cardiac event in the CC group,while age(HR=1.020,95%CI:1.002–1.039,P=0.029)and hemoglobin(HR=0.844,95%CI:0.734–0.970,P=0.017)were independent predictors of all-cause *** survival classification and regression tree analysis showed the optimal cut-off points for cardiac event(eGFR:59.9 m L/min per 1.73 m^2)and all-cause death(age,83 years old;hemoglobin,10.1 g/dL)in the CC *** In predicting prognosis,CC showed interactions with several risk *** function,age,and hemoglobin were pivotal markers in HF patients with CC.

关键词： Body mass index Cachexia Heart failure Mortality Prognosis

Effect of double platinum agents, combination of miriplatintransarterial oily chemoembolization and cisplatinhepatic arterial infusion chemotherapy, in patients with hepatocellular carcinoma: Report of two cases

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World Journal of Clinical Cases 2017年第6期5卷 238-246页

作者： Kohei Ogawa Kenya Kamimura Yukari Watanabe Yosuke Motai Daisuke Kumaki Ryoya Seki Akira Sakamaki Satoshi abe Hirokazu Kawai takeshi Suda Satoshi Yamagiwa Shuji Terai Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University Department of Gastroenterology and Hepatology Uonuma Institute of Community Medicine Niigata Medical and Dental Hospital

Hepatocellular carcinoma(HCC) is one of the most common cancers and the third highest cause of cancerassociated mortality worldwide. The treatment of HCC is complicated by its variable biological behavior and the frequent coexistence of chronic liver disease, particularly cirrhosis. To date, multiple treatment modalities have been developed according to the stage of the tumor and the hepatic functional reserve, including transarterial treatments such as transarterial chemoembolization, transarterial oily chemoembolization(TOCE), and hepatic arterial infusion chemotherapy(HAIC). We conducted a phase I and II study of the combination therapy with double platinum agents, miriplatin and cisplatin, and confirmed its safety and efficacy. Here, we describe two cases of unresectable HCC who were successfully treated by miriplatin-TOCE/cisplatin-HAIC combination therapy, resulting in complete responses with no significant adverse events. This report will provide that the combination therapy can be the therapeutic option for HCC patients in the advanced stage.

关键词： Hepatocellular carcinoma Double platinum Transarterial oily chemoembolization Hepatic arterial infusion chemotherapy Combination