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| 1 | Rifaximin ameliorates hepatic encephalopathy and endotoxemia without affecting the gut microbiome diversity显示文摘AIM To determine the efficacy of rifaximin for hepatic encephalopathy(HE) with the linkage of gut microbiome in decompensated cirrhotic patients.METHODS Twenty patients(12 men and 8 women; median age, 66.8 years; range, 46-81 years) with decompensated cirrhosis(Child-pugh score > 7) underwent cognitive neuropsychological testing, endotoxin analysis, and fecal microbiome assessment at baseline and after 4 wk of treatment with rifaximin 400 mg thrice a day. HE was determined by serum ammonia level and number connection test(NCT)-A. Changes in whole blood endotoxin activity(EA) was analyzed by endotoxinactivity assay. Fecal microbiome was assessed by 16 S ribosome RNA(rR NA) gene sequencing.RESULTS Treatment with rifaximin for 4 wk improved hyperammonemia(from 90.6 ± 23.9 μg/d L to 73.1 ± 33.1 μg/dL; P < 0.05) and time required for NCT(from 68.2 ± 17.4 s to 54.9 ± 20.3 s; P < 0.05) in patients who had higher levels at baseline. Endotoxin activity was reduced(from 0.43 ± 0.03 to 0.32 ± 0.09; P < 0.05) in direct correlation with decrease in serum ammonia levels(r = 0.5886, P < 0.05). No statistically significant differences were observed in the diversity estimator(Shannon diversity index) and major components of the gut microbiome between the baseline and after treatment groups(3.948 ± 0.548 at baseline vs 3.980 ± 0.968 after treatment; P = 0.544), but the relative abundances of genus Veillonella and Streptococcus were lowered.CONCLUSION Rifaximin significantly improved cognition and reduced endotoxin activity without significantly affecting the composition of the gut microbiome in patients with decompensated cirrhosis. | Kosuke Kaji Hiroaki Takaya Soichiro Saikawa Masanori Furukawa Shinya Sato Hideto Kawaratani Mitsuteru Kitade Kei Moriya Tadashi Namisaki Takemi Akahane Akira Mitoro Hitoshi Yoshiji | 2017 | World Journal of Gastroenterology2017，23，47： | 14 |
| 2 | Decreased phagocytic activity of Kupffer cells in a rat nonalcoholic steatohepatitis model显示文摘AIM: To investigate Kupffer cell dynamics and phagocytic activity,using a rat nonalcoholic steatohepatitis (NASH) model. METHODS: Male F344 rats were fed either a control diet or a choline-deficient L-amino acid-defined (CDAA) diet,followed by contrast enhanced ultrasonography (CEUS) using Levovist. The uptake of latex beads by the Kupffer cells was determined by fluorescent microscopy. The status of the Kupffer cells was compared between the two groups,using the immunohistochemical staining technique. RESULTS: After 4 or more wk of the CDAA diet,CEUS examination revealed a decrease in the signal intensity,20 min after intravenous Levovist. Fluorescent microscopic examination showed that the uptake of latex beads by the Kupffer cells was reduced at week 1 and 2 in the study group,compared with the controls,with no further reduction after 3 wk. Immunohistochemical staining revealed no significant difference in the Kupffer cell counts between the control group and the CDAA group. CONCLUSION: CEUS examination using Levovist demonstrated reduced contrast effect and phagocytic activity in the liver parenchymal phase,although the Kupffer cell numbers were unchanged,indicating reduced phagocytic function of the Kupffer cells in the rat NASH model. We believe that CEUS examination using Levovist is a useful screening modality,which can detect NASH in fatty liver patients. | Tatsuhiro Tsujimoto Hideto Kawaratani Toshiyuki Kitazawa Toshiko Hirai Hajime Ohishi Mitsuteru Kitade Hitoshi Yoshiji Masahito Uemura Hiroshi Fukui | 2008 | World Journal of Gastroenterology2008，14，39： | 12 |
| 3 | Crosstalk between angiogenesis, cytokeratin-18, and insulin resistance in the progression of non-alcoholic steatohepatitis显示文摘AIM: To elucidate the possible crosstalk between angiogenesis, cytokeratin-18 (CK-18), and insulin resistance (IR) especially in patients with non-alcoholic steatohepatitis (NASH).METHODS: Twenty-eight patients with NASH and 11 with simple fatty liver disease (FL) were enrolled in this study and underwent clinicopathological examination. The measures of angiogenesis, CK-18, and IR employed were CD34-immunopositive vessels, CK-18immunopositive cells, and homeostasis model assessment of IR (HOMA-IR), respectively. The correlations of these factors with NASH were elucidated.RESULTS: Significant development of hepatic neovascularization was observed only in NASH, whereas almost no neovascularization could be observed in FL and healthy liver. The degree of angiogenesis was almost parallel to liver fibrosis development, and both parameters were positively correlated. Similarly, CK-18expression and HOMA-R were signifi cantly increased in NASH as compared with FL and healthy liver. Furthermore, CK-18 and HOMA-IR were also positively correlated with the degree of neovascularization. CONCLUSION: These results indicate that the crosstalk between angiogenesis, CK-18, and IR may play an important role in the onset and progression of NASH. | Mitsuteru Kitade Hitoshi Yoshiji Ryuichi Noguchi Yasuhide Ikenaka Kosuke Kaji Yusaku Shirai Masaharu Yamazaki Masahito Uemura Junichi Yamao Masao Fujimoto Akira Mitoro Masahisa Toyohara Masayoshi Sawai Motoyuki Yoshida Chie Morioka Tatsuhiro Tsujimoto Hideto Kawaratani Hiroshi Fukui | 2009 | World Journal of Gastroenterology2009，15，41： | 9 |
| 4 | Serum angiotensin-converting enzyme level for evaluating significant fibrosis in chronic hepatitis B显示文摘AIM To evaluate the diagnostic performance of angiotensinconverting enzyme(ACE)on significant liver fibrosis in patients with chronic hepatitis B(CHB). METHODS In total,100 patients with CHB who underwent liver biopsy in our hospital were enrolled,and 70 patients except for 30 patients with hypertension,fatty liver or habitual alcoholic consumption were analyzed.We compared histological liver fibrosis and serum ACE levels and evaluated the predictive potential to diagnose significant liver fibrosis by comparison with several biochemical marker-based indexes such as the aspartate aminotransferase(AST)-to-platelet ratio index(APRI),the fibrosis index based on four factors(FIB-4),the Mac-2 binding protein glycosylation isomer(M2BPGi)level and the number of platelets(Plt). RESULTS Serum ACE levels showed moderately positive correlation with liver fibrotic stages(R2=0.181).Patients with significant,advanced fibrosis and cirrhosis(F2-4)had significantly higher serum ACE levels than those with early-stage fibrosis and cirrhosis(F0-1).For significant fibrosis(≥F2),the 12.8 U/L cut-off value of ACE showed 91.7%sensitivity and 75.0%specificity.The receiver-operating characteristic(ROC)curves analysis revealed that the area under the curve(AUC)value of ACE was 0.871,which was higher than that of APRI,FIB-4,M2BPGi and Plt. CONCLUSION The serum ACE level could be a novel noninvasive,easy,accurate,and inexpensive marker of significant fibrosis stage in patients with CHB. | Ryuichi Noguchi Kosuke Kaji Tadashi Namisaki Kei Moriya Mitsuteru Kitade Kosuke Takeda Hideto Kawaratani Yasushi Okura Yosuke Aihara Masanori Furukawa Akira Mitoro Hitoshi Yoshiji | 2017 | World Journal of Gastroenterology2017，23，36： | 6 |
| 5 | Innate immune reactivity of the liver in rats fed a choline-deficient L-amino-acid-defined diet显示文摘瞄准:调查肿瘤坏死 factor-alpha (TNF-alpha ) 的天生的有免疫力的反应,像使用费的受体 4 (TLR4 ) ,并且在非酒精的 steatohepatitis (NASH ) 的肝的 CD14 为老鼠建模。方法:男 F344 老鼠被喂一本胆碱缺乏的 L-amino-acid-defined (CDAA ) 食谱。老鼠在食谱的 4 或 8 wk 以后被打死,并且他们的肝为免疫被移开组织化学的调查和 RNA 抽取。肝标本是为 TNF-alpha, TLR4,和 CD14 染色的免疫。TNF-alpha, TLR4,和 CD14 的基因表情被 reverse-transcriptase 聚合酶链反应(RT-PCR ) 决定。Kupffer 房间被 Percoll 坡度远心沉淀从肝孤立,并且当时是有教养的测量 TNF-alpha 生产。结果:在老鼠作为与控制相比显著地增加了的 CDAA-fed 的 TNF-alpha 的浆液和肝层次组织,,与 steatohepatitis 的前进做了免疫组织化学的值和 TNF-alpha, TLR4,和 CD14 的基因表达式。从 CDAA-fed 老鼠的孤立的 Kupffer 房间的 TNF-alpha 生产被脂肪的多糖刺激提高。结论:TNF-alpha, TLR4,和 CD14 的表情在 NASH 模型增加了,建议 TLR4 和调停 CD14 的内毒素肝损坏可以也发生在 NASH。 | Hideto Kawaratani Tatsuhiro Tsujimoto Toshiyuki Kitazawa Mitsuteru Kitade Hitoshi Yoshiji Masahito Uemura Hiroshi Fukui | 2008 | World Journal of Gastroenterology2008，14，43： | 6 |
| 6 | Combined treatment of vitamin K_2 and angiotensin-converting enzyme inhibitor ameliorates hepatic dysplastic nodule in a patient with liver cirrhosis显示文摘Although it is well known that the hepatocellular carcinoma (HCC) is an ominous complication in patients with liver cirrhosis, there has been no approved drug to prevent the development of HCC to date. We previously reported that the combined treatment of vitamin K2 (VK) and angiotensin-converting enzyme inhibitor (ACE-I) significantly suppressed the experimental hepatocarcinogenesis. A 66-year-old Japanese woman with hepatitis C virus (HCV)-related liver cirrhosis developed a dysplastic nodule in the liver detected by enhanced computed tomography along with elevation of the tumor markers, namely, alpha-fetoprotein (AFP) and lectin-reactive demarcation (AFP-L3), suggesting the presence of latent HCC. After oral administration of VK and ACE-I, the serum levels of both AFP and AFP-L3 gradually decreased without any marked alteration of the serum aminotransferase activity. After one-year treatment, not only the serum levels of AFP and AFP-L3 returned to the normal ranges, but also the dysplastic nodule disappeared. Since both VK and ACE-I are widely used without serious side effects, this combined regimen may become a new strategy for chemoprevention against HCC. | Hitoshi Yoshiji Ryuichi Noguchi Masaharu Yamazaki Yasuhide Ikenaka Masayoshi Sawai Masatoshi Ishikawa Hideto Kawaratani Tsuyoshi Mashitani Mitsuteru Kitade Kosuke Kaji Masahito Uemura Junichi Yamao Masao Fujimoto Akira Mitoro Masahisa Toyohara Motoyuki Yoshida Hiroshi Fukui | 2007 | World Journal of Gastroenterology2007，13，23： | 5 |
| 7 | Dual therapy with zinc acetate and rifaximin prevents from ethanolinduced liver fibrosis by maintaining intestinal barrier integrity显示文摘BACKGROUND Hepatic overload of gut-derived lipopolysaccharide dictates the progression of alcoholic liver disease(ALD)by inducing oxidative stress and activating Kupffer cells and hepatic stellate cells through toll-like receptor 4 signaling.Therefore,targeting the maintenance of intestinal barrier integrity has attracted attention for the treatment of ALD.Zinc acetate and rifaximin,which is a nonabsorbable antibiotic,had been clinically used for patients with cirrhosis,particularly those with hepatic encephalopathy,and had been known to improve intestinal barrier dysfunction.However,only few studies focused on their efficacies in preventing the ALD-related fibrosis development.AIM To investigate the effects of a combined zinc acetate with rifaximin on liver fibrosis in a mouse ALD model.METHODS To induce ALD-related liver fibrosis,female C57BL/6J mice were fed a 2.5%(v/v)ethanol-containing Lieber-DeCarli liquid diet and received intraperitoneal carbon tetrachloride(CCl4)injection twice weekly(1 mL/kg)for 8 wk.Zinc acetate(100 mg/L)and/or rifaximin(100 mg/L)were orally administered during experimental period.Hepatic steatosis,inflammation and fibrosis as well as intestinal barrier function were evaluated by histological and molecular analyses.Moreover,the direct effects of both agents on Caco-2 barrier function were assessed by in vitro assays.RESULTSIn the ethanol plus CCl4-treated mice,combination of zinc acetate and rifaximin attenuated oxidative lipid peroxidation with downregulation of Nox2 and Nox4.This combination significantly inhibited the Kupffer cells expansion and the proinflammatory response with blunted hepatic exposure of lipopolysaccharide and the toll-like receptor 4/nuclear factor kB pathway.Consequently,liver fibrosis and hepatic stellate cells activation were efficiently suppressed with downregulation of Mmp-2,-9,-13,and Timp1.Both agents improved the atrophic changes and permeability in the ileum,with restoration of tight junction proteins(TJPs)by decreasing the expressions of tumor necrosis factorαand myosin light chain kinase.In the in vitro assay,both agents directly reinforced ethanol or lipopolysaccharide-stimulated paracellular permeability and upregulated TJPs in Caco-2 cells.CONCLUSION Dual therapy with zinc acetate and rifaximin may serve as a strategy to prevent ALD-related fibrosis by maintaining intestinal barrier integrity. | Yuki Fujimoto Kosuke Kaji Norihisa Nishimura Masahide Enomoto Koji Murata Soichi Takeda Hiroaki Takaya Hideto Kawaratani Kei Moriya Tadashi Namisaki Takemi Akahane Hitoshi Yoshiji | 2021 | World Journal of Gastroenterology2021，27，48： | 4 |
| 8 | Immunotherapy for nonalcoholic steatohepatitis using the multiple cytokine production modulator Y-40138显示文摘AIM:To investigate the possible use of the multiple cytokine production modulator,Y-40138,as a novel immunotherapy in the rat nonalcoholic steatohepatitis (NASH) model. METHODS:We allocated 6-wk-old male F344 rats to choline-supplemented,L-amino acid-defined (CSAA) diet (control group),CSAA diet + Y-40138 (control + Y-40138 group),choline-def icient,L-amino acid-def ined (CDAA) diet (NASH group),or CDAA diet + Y-40138 (NASH + Y-40138 group). In each group,we measured the plasma alanine aminotransferase (ALT) levels,and the plasma and liver levels of tumor necrosis factor-α (TNF-α),interferon-γ (IFN-γ),and interleukin-10 (IL-10). Tissue specimens of phosphate buffered saline-perfused liver were subjected to hematoxylin and eosin staining,Azan staining,Sirius red staining,and immunohistochemical staining (for Kupffer cells and TNF-α). We then extracted Kupffer cells from the collagenase-perfused livers using the Percoll gradient centrifugation method,and measured the TNF-α levels in the supernatant (in vitro TNF-α production by Kupffer cells) using an enzyme-linked immunosorbent assay kit.RESULTS:In comparison to the NASH group,serumALT elevation was mild,production of serum and liver TNF-α and IFN-γ was inhibited,and IL-10 production was increased in the NASH + Y-40138 group. Amelioration of liver histology was also noted in the NASH + Y-40138 group. Kupffer cell immunohistochemical staining revealed no differences between groups,whereas TNF-α immunohistochemical staining showed fewer stained cells in the NASH + Y-40138 group than in the NASH group. The TNF-α levels in the in-vitro Kupffer cell culture supernatant were lower in the NASH + Y-40138 group than in the NASH group.CONCLUSION:Administration of Y-40138 to NASH model rats reduced hepatic inflammation and suppressed fibrosis. These results indicate that the multiple cytokine production modulator,Y-40138,is promising as a novel treatment for NASH. | Tatsuhiro Tsujimoto Hideto Kawaratani Toshiyuki Kitazawa Hitoshi Yoshiji Masao Fujimoto Masahito Uemura Hiroshi Fukui | 2009 | World Journal of Gastroenterology2009，15，44： | 4 |
| 9 | Eosinophilic cholecystitis along with pericarditis caused by Ascaris lumbricoides: A case report显示文摘Although the etiology of eosinophilic cholecystitis is still obscure, the postulated causes include allergies, parasites, hypereosinophilic syndrome, and eosinophilic gastroenteritis. It is sometimes accompanied by several complications, but a simultaneous onset with pericarditis is very rares. A 28-year-old woman complained of acute right hypocondrial pain and dyspnea associated with systemic eruption. Several imaging modalities revealed acute cholecystitis and pericarditis with massive pericardial effusion. A marked peripheral blood eosinophilia was observed, and the eruption was diagnosed as urticaria. Her serum had a high titer of antibody against Ascaris lumbricoides . Treatment with albendazole drastically improved all clinical manifestations along with normalization of the imaging features and eosinophilia. We report herein a rare case of simultaneous onset of acute cholecystitis and pericarditis associated with a marked eosinophilia caused by parasitic infection. | Kosuke Kaji Hitoshi Yoshiji Masahide Yoshikawa Masaharu Yamazaki Yasuhide Ikenaka Ryuichi Noguchi Masayoshi Sawai Masatoshi Ishikawa Tsuyoshi Mashitani Mitsuteru Kitade Hideto Kawaratani Masahito Uemura Junichi Yamao Masao Fujimoto Akira Mitoro Masahisa Toyohara Motoyuki Yoshida Hiroshi Fukui | 2007 | World Journal of Gastroenterology2007，13，27： | 3 |
| 10 | 尼可地尔经皮冠状动脉介入治疗(PCI)降低心肌损伤显示文摘背景尼可地尔作为辅助治疗药物,在缺血性心脏病患者的治疗中具有良好效果。本研究旨在评估尼可地尔选择性经皮冠状动脉治疗(PCI)后对心肌的保护作用。方法我们随机地将49个接受选择性PCI治疗的病人分为尼可地尔及对照这两组。PCI治疗前,尼可地尔组先静脉推注4mg尼可地尔,介入治疗后再以6mg每小时的量静脉滴注24小时。口服尼可地尔给药组持续给药直至接下来的冠状动脉造影(CAG)。PCI治疗前及PCI治疗后0、4、24及48小时分别采集各组静脉血样,检测肌酸激酶(CK)、肌酸激酶MB亚型(CK-MB)、肌钙蛋白Ⅰ(TnI)和肌红蛋白的量。通过对比治疗前后的脑室造影来评价左心室功能及左心室壁运动。结果 PCI治疗后24小时,尼可地尔组的心肌酶水平显著低于对照组;实验组及对照组的CK分别为78.1±34.9,117.4±137.9U/l,显著性P=0.0141,CK-MB为1.57±1.90,2.67±4.50U/l,显著性P=0.0485,TnI为0.37±0.55,0.86±1.65ng/ml,显著性P=0.0101。尼可地尔组的局部左心室壁运动在后期较对照组显著增强。结论尼可地尔能抑制选择性PCI治疗后心肌酶的水平,并在后期显著增强左心室壁的运动,表明尼可地尔可提高PCI治疗时对心肌的保护,降低因血管成形术造成的心肌损伤。 | Tsuyoshi Isono Hiroshi Kamihata Yasuo Sutani Masayuki Motohiro Satoshi Yamamoto Shiori Kyoui Yoshiji Iharada Kouji Kurimoto Katsuko Hara Hakuo Takahashi Toshiji Iwasaka 陈浩 | 2016 | 首都食品与医药2016，23，20： | 3 |
| 11 | Analysis of Ship Evacuation during Tsunami Using AIS (Automatic Identification System) Data显示文摘 | Masao Furusho Yoshiji Yano | 2012 | Journal of Earth Science and Engineering2012，2，7： | 2 |
| 12 | Tissue inhibitors of metalloproteinases: Structure regulation and biological functions显示文摘 | Gomez DE Alonso DF Yoshiji H | 1997 | Eur J Cell Biol1997，74，2： | 2 |
| 13 | Combination of vitamin K 2 and angiotensin-converting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma显示文摘 | Hitoshi Yoshiji Ryuichi Noguchi Masahisa Toyohara Yasuhide Ikenaka Mitsuteru Kitade Kosuke Kaji Masaharu Yamazaki Junichi Yamao Akira Mitoro Masayoshi Sawai Motoyuki Yoshida Masao Fujimoto Tatsuhiro Tsujimoto Hideto Kawaratani Masahito Uemura Hiroshi Fuku | 2009 | Journal of Hepatology2009，，2： | 2 |
| 14 | Interferon augments the anti-fibrotic activity of an angiotensin-converting enzyme inhibitor in patients with refractory chronic hepatitis C显示文摘AIM: To evaluate the effect of combination treatment with the interferon (IFN) and angiotensin-converting enzyme inhibitor (ACE-Ⅰ) on several fibrotic indices in patients with refractory chronic hepatitis C (CHC). METHODS: Perindopril (an ACE-Ⅰ; 4 mg/d) and/or natural IFN (3 MU/L; 3 times a week) were administered for 12 mo to refractory CHC patients, and several indices of serum fibrosis markers were analyzed. RESULTS: ACE-Ⅰdecreased the serum fibrosis markers, whereas single treatment with IFN did not exert these inhibitory effects. However, IFN significantly augmented the effects of ACE-Ⅰ, and the combination treatment exerted the most potent inhibitory effects. The serum levels of alanine transaminase and HCV-RNA were not significantly different between the groups, whereas the plasma level of transforming growth factor-b was significantly attenuated almost in parallel with suppression of the serum fibrosis markers. CONCLUSION: The combination therapy of an ACE- Ⅰand IFN may have a diverse effect on disease progression in patients with CHC refractory to IFN therapy through its anti-fibrotic effect. | Hitoshi Yoshiji Ryuichi Noguchi Hideyuki Kojima Yasuhide Ikenaka Mitsuteru Kitade Kosuke Kaji Masahito Uemura Junichi Yamao Masao Fujimoto Masaharu Yamazaki Masahisa Toyohara Akira Mitoro Hiroshi Fukui | 2006 | World Journal of Gastroenterology2006，12，42： | 2 |
| 15 | Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats显示文摘 | Hitoshi Yoshiji Shigeki Kuriyama Junichi Yoshii Yasuhide Ikenaka Ryuichi Noguchi Toshiya Nakatani Hirohisa Tsujinoue Hiroshi Fukui | 2001 | Hepatology2001，，4： | 2 |
| 16 | Production of virus--free plantlets by anther culture of lilium × ' Enchantment '显示文摘 | YOSHIJI N DONG-SHENG H MAKOTO F | 2001 | Scientia Horticulturae2001，90，： | 1 |
| 17 | Amelioration of carcinogenesis and tumor growth in the rat liver by combination of vitamin K2 and angiotensin-converting enzyme inhibitor via anti-angiogenic activities显示文摘 | Yoshiji H Kuriyama S Noguchi R | 2006 | Oncol Rep2006，15，1： | 1 |
| 18 | Vascular endotheli- al growth factor and receptor interaction is a prerequisite for mu- rine hepatic fibrogenesis显示文摘 | YOSHIJI H KURIYAMA S YOSHII J | 2003 | Gut2003，52，9： | 1 |
| 19 | Relationship between the proliferative capability of hepatocytes andthe intrahepatic expression of hepatocyte growth factor and c-Met in the courseof cirrhosis development in rats显示文摘 | Hideyuki Inoue Fumi Yokoyama Yuko Kita Hitoshi Yoshiji Tatsuhiro Tsujimoto Akihiro Deguchi Seiji Nakai Asahiro Morishita Naohito Uchida Tsutomu Masaki Seishiro Watanabe Shigeki Kuriyama | 2006 | International Journal of Molecular Medicine2006，，5： | 1 |
| 20 | Tissue inhibitor ofmetaloproteinases-1 attenuates spontaneous liver fibrosisresolution in the transgenic mouse显示文摘 | Yoshiji H Kuriyama S Yoshii J | 2002 | Hepawlogy2002，36，41： | 1 |
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