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1Association of Fusobacterium nucleatum with immunity andmolecular alterations in colorectal cancer显示文摘The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum(F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6%(44/511), which was lower than that in United States cohort studies(13%). Similar to the United States studies, F. nucleatum positivityin Japanese colorectal cancers was significantly associated with microsatellite instability(MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets(i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain micro RNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. Micro RNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in colorectal cancer cells. Thus, emerging evidence may provide insights for strategies to target microbiota, immune cells and tumor molecular alterations for colorectal cancer prevention and treatment. Further investigation is needed to clarify the association of Fusobacterium with T-cells and micro RNA expressions in colorectal cancer.Katsuhiko Nosho Yasutaka Sukawa Yasushi Adachi Miki Ito Kei Mitsuhashi Hiroyoshi Kurihara Shinichi Kanno Itaru Yamamoto Keisuke Ishigami Hisayoshi Igarashi Reo Maruyama Kohzoh Imai Hiroyuki Yamamoto Yasuhisa Shinomura 2016World Journal of Gastroenterology2016,22,2:44
2Diagnostic and therapeutic single-operator cholangiopancreatoscopy in biliopancreatic diseases:Prospective multicenter study in Japan显示文摘AIM: To assess the utility and safety of single-operator cholangiopancreatoscopy(SOCPS) using the Spy Glass system in widespread clinical application for biliary and pancreatic diseases.METHODS: This study was a prospective case series conducted in 20 referral centers in Japan. There were 148 patients who underwent SOCPS; 124 for biliary diseases and 24 for pancreatic diseases. The attempted interventions were SOCPS examination, SOCPS-directed tissue sampling, and therapy for stone removal, among others. The main outcomes were related to the procedure success rate in terms of visualizing the target lesions, SOCPS-directed adequate tissue sampling, and complete stone removal. RESULTS: A total of 148 patients were enrolled for the diagnosis of indeterminate biliary and pancreatic lesions or treatment of biliary and pancreatic disease. The overall procedure success rate of visualizing the target lesions was 91.2%(135/148). The overall procedural success rates of visualizing the target lesions of diagnostic SOCPS in the bile duct and pancreatic duct were 95.5%(84/89) and 88.2%(15/17), respectively. Diagnosis: the overall adequate tissue for histologic examination was secured in 81.4% of the 86 patients who underwent biopsy under SOCPS(bile duct, 60/75, 80.0%; pancreatic duct, 10/11, 90.9%). The accuracy of histologic diagnosis using SOCPS-directed biopsies in indeterminate bile duct lesions was 70.7%(53/75). In the pancreatic duct, the accuracy of SOCPS visual impression of intraductal papillary mucinous neoplasm was 87.5%(14/16). Stone therapy: complete biliary and pancreatic stone clearance combined with SOCPS-directed stone therapy using electrohydraulic lithotripsy or laser lithotripsy was achieved in 74.2%(23/31) and 42.9%(3/7) of the patients, respectively. Others: SOCPS using the Spy Glass system was used in cannulation of the cystic duct in two patients and for passing across the obstructed self-expandable metallic stent for a malignant biliary stricture in two patients. All procedures were successful in both SOCPS-guided therapies. The incidence of procedure-related adverse events was 5.4%(8/148). CONCLUSION: SOCPS with direct visualization and biopsy for diagnosis and SOCPS-directed therapy for biliary and pancreatic diseases can be safely performed with a high success rate.Toshio Kurihara Ichiro Yasuda Hiroyuki Isayama Toshio Tsuyuguchi Taketo Yamaguchi Ken Kawabe Yoshinobu Okabe Keiji Hanada Tsuyoshi Hayashi Takao Ohtsuka Syuhei Oana Hiroshi Kawakami Yoshinori Igarashi Kazuya Matsumoto Kiichi Tamada Shomei Ryozawa Hiroki Kawashima Yutaka Okamoto Iruru Maetani Hiroyuki Inoue Takao Itoi 2016World Journal of Gastroenterology2016,22,5:20
3Anti-Inflammatory Effects of Redlining Injection (热毒宁注射液)on Lipopolysaccharide-lnduced Acute Lung Injury of Rats显示文摘Objective:To evaluate the protective effects of Reduning Injection(热毒宁注射液.RON),a patent Chinese medicine,on lipopolysaccharide(LPS)-induced acute lung injury(ALI)in rats and its underlying mechanisms of action.Methods:Sixty male Sprague-Dawley rats were randomly divided into 6 groups,including normal control,model,dexamethasone(DEX,5 mg/kg),RDN-H(720 mg/kg),RDN-M(360 mg/kg)and RDN-L(180 mg/kg)groups,with 10 rats in each group.Rats were challenged with intravenous injection of LPS 1 h after intraperitoneal treatment with RDN or DEX.At 6 h after LPS challenge,lung tissues and bronchoaiveolar lavage fluid(BALF)were collected,and the number of inflammatory cells was determined.The right lungs were collected for histopathologic examination,measurement of gene and protein expressions,superoxide dismutase(SOD)and myeloperoxidase(MPO)activities.Results:In vivo pretreatment of RDN(360,720 mg/kg)significantly reduced the weight of wet to dry(W/D)ratio of lung,protein content in BALF,and led to remarkable attenuation of LPS-induced histopathological changes in the lungs.Meanwhile,RDN enormously decreased BALF total inflammatory cells,especially neutrophil and macrophage cell numbers.Moreover,RDN increased SOD activity,inhibited MPO activity,alleviated LPS-induced tumor neurosis factor-α(TNF-α)and inducible nitric oxide synthase(iNOS)expression in lung tissues.Furthermore,RDN(720 mg/kg)efficiently weakened nuclear factorkappa B(NF-κB)gene and protein expression.Conclusion:Anti-inflammatory effects of RDN was demonstrated to be preventing pulmonary neutrophil infiltration,lowering MPO activity,TNF-αand iNOS gene expression by inhibiting NF-κB activity in LPS-induced ALI.唐陆平 萧伟 李怡芳 李海波 王振中 姚新生 Hiroshi Kurihara 何蓉蓉 2014Chinese Journal of Integrative Medicine2014,20,8:14
4Endoscopic ultrasound-guided choledochoduodenostomy in patients with failed endoscopic retrograde cholangiopancreatography显示文摘Endoscopic ultrasonography (EUS)-guided biliary drainage was performed for treatment of patients who have obstructive jaundice in cases of failed endoscopic retrograde cholangiopancreatography (ERCP). In the present study,we introduced the feasibility and outcome of EUS-guided choledochoduodenostomy in four patients who failed in ERCP. We performed the procedure in 2 papilla of Vater,including one resectable case,and 2 cases of cancer of the head of pancreas. Using a curved linear array echoendoscope,a 19 G needle or a needle knife was punctured transduodenally into the bile duct under EUS visualization. Using a biliary catheter for dilation,or papillary balloon dilator,a 7-Fr plastic stent was inserted through the choledochoduodenostomy site into the extrahepatic bile duct. In 3 (75%) of 4 cases,an indwelling plastic stent was placed,and in one case in which the stent could not be advanced into the bile duct,a naso-biliary drainage tube was placed instead. In all cases,the obstructive jaundice rapidly improved after the procedure. Focal peritonitis and bleeding not requiring blood transfusion was seen in one case. In this case,pancreatoduodenectomy was performed and the surgical findings revealed severe adhesion around the choledochoduodenostomy site. Although further studies and development of devices are mandatory,EUS-guided choledochoduodenostomy appears to be an effective alternative to ERCP in selected cases.Takao Itoi Fumihide Itokawa Atsushi Sofuni Toshio Kurihara Takayoshi Tsuchiya Kentaro Ishii Shujiro Tsuji Nobuhito Ikeuchi Fuminori Moriyasu 2008World Journal of Gastroenterology2008,14,39:13
5Hepatic steatosis as a possible risk factor for the development of hepatocellular carcinoma after eradication of hepatitis C virus with antiviral therapy in patients with chronic hepatitis C显示文摘AIM: To elucidate risk factors contributing to the development of hepatocellular carcinoma (HCC) among patients with sustained viral response (SVR) after interferon (IFN) treatment and to examine whether HCV-RNA still remained in the liver of SVR patients who developed HCC. METHODS: Two-hundred and sixty-six patients, who achieved SVR, were enrolled in this study. We retrospectively reviewed clinical, viral and histological features of the patients, and examined whether the development of HCC depends on several clinical variables using Kaplan-Meier Method. RT-PCR was used to seek HCV-RNA in 3 out of 7 patients in whom liver tissue was available for molecular analysis. RESULTS: Among the enrolled 266 patients with SVR, HCC developed in 7 patients (7/266; 2.6%). We failed to detect HCV-RNA both in cancer and non-cancerous liver tissue in all three patients. The cumulative incidence for HCC was significantly different depending on hepatic fibrosis (F3-4) (P = 0.0028), hepatic steatosis (Grade 2-3) (P = 0.0002) and age (≥ 55) (P = 0.021) at the pre-interferon treatment. CONCLUSION: The current study demonstrated that age, hepatic fibrosis, and hepatic steatosis at pre- interferon treatment might be risk factors for developing HCC after SVR.Atsushi Tanaka Satoko Uegaki Hiroko Kurihara Kiyoshi Aida Masaki Mikami Ikuo Nagashima Junji Shiga Hajime Takikawa 2007World Journal of Gastroenterology2007,13,39:12
6Safety trial of high-intensity focused ultrasound therapy for pancreatic cancer显示文摘AIM:To evaluate the safety and clinical application of high-intensity focused ultrasound(HIFU)therapy for unresectable pancreatic cancer(PC).METHODS:Thirty PC patients(16 cases in stage III and 14 cases in stage IV)with visualized pancreatic tumors were admitted for HIFU therapy as an optional local therapy in addition to systemic chemotherapy or chemoradiotherapy.Informed consent was obtained.This study began at the end of 2008 and was approved by the ethics committee of our hospital[Institutional Review Board(IRB):890].The HIFU device used was the FEP-BY02(Yuande Bio-Medical Engineering,Beijing,China).RESULTS:The mean tumor size after HIFU therapy changed to 30.9±1.7 mm from 31.7±1.7 mm at pre-therapy.There were no significant changes in tumor size,mean number of treatment sessions(2.7±0.1 mm),or mean total treatment time(2.4±0.1 h).The rate of symptom relief effect was 66.7%.The effectiveness of primary lesion treatment was as follows:complete response,0;partial response,4;stable disease,22;progressive disease,4.Treatment after HIFU therapy included 2 operations,24 chemotherapy treatments,and 4 best supportive care treatments.Adverse events occurred in 10%of cases,namely pseudocyst formation in 2 cases and mild pancreatitis development in 1.However,no severe adverse events occurred in this study.CONCLUSION:We suggest that HIFU therapy is safe and has the potential to be a new method of combination therapy for PC.Atsushi Sofuni Fuminori Moriyasu Takatomo Sano Fumihide Itokawa Takayoshi Tsuchiya Toshio Kurihara Kentaro Ishii Syujiro Tsuji Nobuhito Ikeuchi Reina Tanaka Junko Umeda Ryosuke Tonozuka Mitsuyoshi Honjo Shuntaro Mukai Mitsuru Fujita Takao Itoi 2014World Journal of Gastroenterology2014,20,28:12
7Autophagy-dependent removal of α-synuclein: a novel mechanism of GM1 ganglioside neuroprotection against Parkinson’s disease显示文摘GM1 ganglioside is particularly abundant in the mammalian central nervous system and has shown beneficial effects on neurodegenerative diseases.In this study,we investigated the therapeutic effect of GM1 ganglioside in experimental models of Parkinson’s disease(PD)in vivo and in vitro.Mice were injected with MPTP(30 mg·kg-1·d−1,i.p.)for 5 days,resulting in a subacute model of PD.PD mice were treated with GM1 ganglioside(25,50 mg·kg^(−1)·d^(−1),i.p.)for 2 weeks.We showed that GM1 ganglioside administration substantially improved the MPTP-induced behavioral disturbance and increased the levels of dopamine and its metabolites in the striatal tissues.In the MPP^(+)-treated SH-SY5Y cells andα-synuclein(α-Syn)A53T-overexpressing PC12(PC12^(α-Syn A53T))cells,treatment with GM1 ganglioside(40μM)significantly decreasedα-Syn accumulation and alleviated mitochondrial dysfunction and oxidative stress.We further revealed that treatment with GM1 ganglioside promoted autophagy,evidenced by the autophagosomes that appeared in the substantia nigra of PD mice as well as the changes of autophagy-related proteins(LC3-II and p62)in the MPP^(+)-treated SH-SY5Y cells.Cotreatment with the autophagy inhibitor 3-MA or bafilomycin A1 abrogated the in vivo and in vitro neuroprotective effects of GM1 ganglioside.Using GM1 ganglioside labeled with FITC fluorescent,we observed apparent colocalization of GM1-FITC andα-Syn as well as GM1-FITC and LC3 in PC12^(α-Syn A53T)cells.GM1 ganglioside significantly increased the phosphorylation of autophagy regulatory proteins ATG13 and ULK1 in doxycycline-treated PC12^(α-Syn A53T)cells and the MPP^(+)-treated SH-SY5Y cells,which was inhibited by 3-MA.Taken together,this study demonstrates that the anti-PD role of GM1 ganglioside resulted from activation of autophagy-dependentα-Syn clearance.Yu-Lin Guo Wen-Jun Duan Dan-Hua Lu Xiao-Hui Ma Xiao-Xiao Li Zhao Li Wei Bi Hiroshi Kurihara Hai-Zhi Liu Yi-Fang Li Rong-Rong He 2021Acta Pharmacologica Sinica2021,42,4:7
8Endoscopic resection of carcinoid of the minor duodenalpapilla显示文摘We encountered a 65-year-old man with a carcinoid tumor of the minor duodenal papilla. Since he had liver cirrhosis and completely refused surgery, we performed an endoscopic snare papillectomy. The papillectomy was performed successfully without procedure-related complication. The specimens revealed a carcinoid tumor showing that the margin of the tumor was positive. One week later, upper GI endoscopy was performed and the biopsy specimens obtained from base of ulcer showed no neoplastic cells. We performed a duodenoscopy and CT 3, 6 and 18 mo later, and there was no macroscopic or microscopic evidence of tumor recurrence after more than 4 years.Takao Itoi Atsushi Sofuni Fumihide Itokawa Takayoshi Tsuchiya Toshio Kurihara Fuminori Moriyasu 2007World Journal of Gastroenterology2007,13,27:6
9Endoscopic papillary large balloon dilation for removal of bile duct stones显示文摘AIM:To investigate the efficacy and outcomes of endoscopic papillary large balloon dilation(EPLBD)for bile duct stones in a multicenter prospective study.METHODS:Lithotomy by EPLBD was conducted in 124patients with bile duct stones≥13 mm in size or with three or more bile duct stones≥10 mm.After endoscopic sphincterotomy,the papilla was dilated using balloons 12-20 mm in diameter fitting the bile duct diameter.RESULTS:The success rate of first-time lithotomy was 86.3%(107/124)and the final lithotomy success rate was 100%(124/124).Lithotripsy was needed in10 of the 124(13.6%)patients.Adverse events due to the treatment procedure occurred in 6(4.8%)patients,all of which were mild.Performing large balloon dilation after endoscopic sphincterotomy in patients with large stones or multiple stones in the bile duct is considered to ensure the safety of treatment and to reduce the need for lithotripsy.CONCLUSION:It is suggested that treatment by EPLBD for large bile duct stones may be safe and useful.Yuji Sakai Toshio Tsuyuguchi Yoshiaki Kawaguchi Nobuto Hirata So Nakaji Katsuya Kitamura Shigeru Mikami Tatsuya Fujimoto Masashi Ijima Eishin Kurihara Shuhei Oana Takayoshi Nishino Ryo Tamura Dai Sakamoto Masato Nakamura Takao Nishikawa Harutoshi Sugiyama Hitoshi Yoshida Tetsuya Mine Osamu Yokosuka 2014World Journal of Gastroenterology2014,20,45:6
10Novel insights into stress-induced susceptibility to influenza:corticosterone impacts interferon-βresponses by Mfn2-mediated ubiquitin degradation of MAVS显示文摘Although stress has been known to increase the susceptibility of pathogen infection,the underlying mechanism remains elusive.In this study,we reported that restraint stress dramatically enhanced the morbidity and mortality of mice infected with the influenza virus(H1N1)and obviously aggravated lung inflammation.Corticosterone(CORT),a main type of glucocorticoids in rodents,was secreted in the plasma of stressed mice.We further found that this stress hormone significantly boosted virus replication by restricting mitochondrial antiviral signaling(MAVS)protein-transduced IFN-βproduction without affecting its mRNA level,while the deficiency of MAVS abrogated stress/CORT-induced viral susceptibility in mice.Mechanistically,the effect of CORT was mediated by proteasome-dependent degradation of MAVS,thereby resulting in the impediment of MAVS-transduced IFN-βgeneration in vivo and in vitro.Furthermore,RNA-seq assay results indicated the involvement of Mitofusin 2(Mfn2)in this process.Gain-and loss-offunction experiments indicated that Mfn2 interacted with MAVS and recruited E3 ligase SYVN1 to promote the polyubiquitination of MAVS.Co-immunoprecipitation experiments clarified an interaction between any two regions of Mfn2(HR1),MAVS(C-terminal/TM)and SYVN1(TM).Collectively,our findings define the Mfn2-SYVN1 axis as a new signaling cascade for proteasome-dependent degradation of MAVS and a‘fine tuning’of antiviral innate immunity in response to influenza infection under stress.Zhuo Luo Li-Fang Liu Ying-Nan Jiang Lu-Ping Tang Wen Li Shu-Hua Ouyang Long-Fang Tu Yan-Ping Wu Hai-Biao Gong Chang-Yu Yan Shan Jiang Yu-Hui Lu Tongzheng Liu Zhenyou Jiang Hiroshi Kurihara Yang Yu Xin-Sheng Yao Yi-Fang Li Rong-Rong He 2020Signal Transduction and Targeted Therapy2020,5,1:5
11Effect of lamivudinein in BeAg-positive chronic hepatitis B: Discordant effect on HBeAg and HBV DNA according to pretreatment ALT level显示文摘AIM: To clarify differences in antiviral effect of the drug in patients with different ALT levels, we examined the changes in HBV markers in patients with high or low ALT levels with or without lamivudine treatment. METHODS: Thirty-seven HBeAg-positive patients were studied. Ten patients with ALT levels higher than 200 IU/L (group 1) and 8 patients with ALT below 200 IU/L (group 2) were treated orally with 100 mg/d of lamivudine. As untreated control, 9 patients with ALT above 200 IU/L (group 3) and 10 patients with ALT below 200 IU/L (group 4) were examined. ALT level, HBeAg/HBeAb status, and HBV DNA level were examined monthly for 11.9±0.4 mo.RESULTS: The ALT level normalized in all 10 patients of group 1, 7/8 of group 2, 4/9 of group 3, and 1/10 of group 4 within 6 mo (groups 1 vs 2, P = NS; groups 1 vs 3, P = 0.002; groups 1vs 4, P<0.0001). HBV DNA fell below the detection limit in all 10 patients of group 1, 7/8 of group 2, 0/9 of group 3, and 0/10 of group 4 within 6 mo (groups 1 vs 2, P = NS). HBeAg became seronegative in 7/10 patients of group 1, 1/8 of group 2, 3/9 of group 3, and 0/10 of group 4 within 12 mo (groups 1 vs2, P= 0.02;groups 1 vs 3, P = NS).CONCLUSION: Our data suggest that HBeAg-positive patients with higher ALT levels can be considered good candidates for lamivudine therapy, probably because lamivudine accelerates the natural seroconversion of HBeAg, accompanied by HBV DNA loss, in these patients.Tomoko Kurihara Fumio Imazeki Osamu Yokosuka Kenichi Fukai Tatsuo Kanda Shigenobu Kawai Hiromitsu Saisho 2005World Journal of Gastroenterology2005,11,22:5
12REM睡眠剥夺对大鼠焦虑行为的影响及瘦素的作用显示文摘目的:研究REM睡眠剥夺对大鼠焦虑行为的影响及瘦素的作用。方法:成年雄性Wistar大鼠90只随机分为9组(n=10),分别为生理盐水群居对照(Ns)24h、72h、120h组;生理盐水REM睡眠剥夺(NSSD)24h、72h、120h组和瘦素REM睡眠剥夺(L—SD)24h、72h、120h组。均为腹腔注射给药。大鼠的REM睡眠剥夺模型采用小平台水环境法建立,大鼠的焦虑行为采用高架十字迷宫(elevatedplus—maze,EPM)测试,分别观察瘦素和生理盐水对REM睡眠剥夺(SD)大鼠(第24、72、120小时)焦虑行为的影响。结果:成功建立REM睡眠剥夺模型及高架十字迷宫焦虑模型。大鼠焦虑行为结果:(1)与NS组相比.NS.SD组在24h(F=5.32,P=0.01)和120h(F=15.06,P=0.00)时EPM的总次数增加,L=SD组在120h时的总次数降低;(2)NS=SD组在120h时的开臂次数%(X2=21.55,P=0.00)和开臂时间%(X2=22.53,P=0.00)均显著增加。L=SD组在120h时的开臂次数%和开臂时间%显著减少。结论:REM睡眠剥夺与大鼠焦虑行为的变化呈时间相关性,瘦素可减少长期REM睡眠剥夺导致的大鼠焦虑行为。因此.瘦素可能参与了REM睡眠剥夺的抗焦虑作用。潘集阳 田径 马文彬 黄俏庭 张继辉 Hiroshi Kurihara 2010实用医学杂志2010,26,13:5
13Vulnerable atherosclerotic plaque features:findings from coronary imaging显示文摘Pathological studies have suggested that features of vulnerable atherosclerotic plaques likely to progress and lead to acute cardiovascular events have specific characteristics.Given the progress of intravascular coronary imaging technology,some large prospective studies have detected features of vulnerable atherosclerotic plaques using these imaging modalities.However,the rate of cardiovascular events,such as acute coronary syndrome,has been found to be considerably reduced in the limited follow-up period available in the statin era.Additionally,not all disrupted plaques lead to thrombus formation with clinical presentation.If sub-occlusive or occlusive thrombus formation does not occur,a thrombus on a disrupted plaque will organize without any symptoms,forming a'healed plaque'.Although vulnerable plaque detection using intracoronary imaging is focused on'thin-cap fibroatheroma'leading to plaque rupture,superficial plaque erosion is increasingly recognized;however,the underlying mechanism of thrombus formation on eroded plaques is not well understood.One of intravascular imaging,optical coherence tomography(OCT)has the highest image resolution and has enabled detailed characterization of the plaque in vivo.Here,we reviewed the status and limitations of intravascular imaging in terms of detecting vulnerable plaque through mainly OCT studies.We suggested that vulnerable plaque should be reconsidered in terms of eroded plaque and healed plaque and that both plaque and circulating blood should be assessed in greater detail accordingly.Osamu Kurihara Masamichi Takano Yasushi Miyauchi Kyoichi Mizuno Wataru Shimizu 2021Journal of Geriatric Cardiology2021,18,7:5
14Coronary atherosclerosis is already ongoing in pre-diabetic status: Insight from intravascular imaging modalities显示文摘Diabetes mellitus is a powerful risk factor of coronary artery disease(CAD), leading to death and disability. In recent years, given the accumulating evidence that prediabetes is also related to increasing risk of CAD including cardiovascular events, a new guideline has been proposed for the treatment of blood cholesterolfor primary prevention of cardiovascular events. This guideline recommends aggressive lipid-lowering statin therapy for primary prevention in diabetes and other patients. The ultimate goal of patient management is to inhibit progression of systemic atherosclerosis and prevent fatal cardiovascular events such as acute coronary syndrome(ACS). Because disruption of atherosclerotic coronary plaques is a trigger of ACS, the high-risk atheroma is called a vulnerable plaque. Several types of novel diagnostic imaging technologies have been developed for identifying the characteristics of coronary atherosclerosis before the onset of ACS, especially vulnerable plaques. According to coronary angioscopic evaluation, atherosclerosis severity and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable to that in diabetic patients. In addition, pharmacological intervention by statin therapy changed plaque color and complexity, and the dynamic changes in plaque features are considered plaque stabilization. In this article, we review the findings of atherosclerosis in prediabetes, detected by intravascular imaging modalities, and the therapeutic implications.Osamu Kurihara Masamichi Takano Yoshihiko Seino Wataru Shimizu Kyoichi Mizuno 2015World Journal of Diabetes2015,6,1:4
15Temporary pancreatic stent to prevent post endoscopic retrograde cholangiopancreatography pancreatitis: a preliminary, single-center, randomized controlled trial显示文摘Takayoshi Tsuchiya Takao Itoi Atsushi Sofuni Fumihide Itokawa Toshio Kurihara Kentaro Ishii Syujiro Tsuji Takashi Kawai Fuminori Moriyasu 2007Journal of Hepato - Biliary - Pancreatic Surgery2007,,3:4
16Prognosis of cancer with branch duct type IPMN of the pancreas显示文摘AIM:To examine the coexistence of metachronous and synchronous cancer in branch duct intraductal papillary mucinous neoplasms of the pancreas (IPMN).METHODS: We reviewed the records of 145 patients with branch duct IPMN between January 1991 and April 2008 and assessed the relationship between IPMN and intraor extra-pancreatic carcinoma and the outcome of IPMN.RESULTS: The mean observation period was 55.9 ± 45.3 mo. Among the 145 patients, the frequency of extra-pancreatic cancer was 29.0%. The frequency of gastric cancer, colon cancer, breast cancer, and pan-creatic cancer were 25.5%, 15.7%, 13.7%, and 9.8%, respectively. Twenty (13.8%) of the patients died. The cause of death was extra-pancreatic carcinoma in 40%,pancreatic cancer in 25%, IPMN per se in 20%, and benign disease in 15% of the patients.CONCLUSION: The prognosis for IPMN depends not on the IPMN per se, but on the presence of intraor extra-pancreatic cancer.Nobuhito Ikeuchi Takao Itoi Atsushi Sofuni Fumihide Itokawa Takayoshi Tsuchiya Toshio Kurihara Kentaro Ishii Shujiro Tsuji Junko Umeda Fuminori Moriyasu Akihiko Tsuchida Kazuhiko Kasuya 2010World Journal of Gastroenterology2010,16,15:3
17Usefulness of contrast-enhanced ultrasonography in determining treatment efficacy and outcome after pancreatic cancer chemotherapy显示文摘AIM:To investigate if contrast-enhanced ultrasonography(CE-US) is useful for determining treatment efficacy and outcome in the early stages of pancreatic cancer chemotherapy by assessing changes in intratumor hemodynamics using CE-US with a contrast agent.METHODS:The subjects were 34 patients with unresectable advanced pancreatic cancer treated by chemotherapy.CE-US was assessed after every treatment(course) completion under the same conditions,and patients were divided into two groups according to the intratumor enhancement pattern:Vascular rich(R) group and vascular poor(P) group.RESULTS:After the second course of treatment,R group in intratumor hemodynamics had 18 patients,and P group had 16 patients.The reduction rates of serum CA19-9 level after chemotherapy which decreased to half or less of the baseline level were 2/15(0.1%) in P group,but 11/16(69%) in R group(P = 0.006).When the mean number of courses of chemotherapy and outcome were compared,P group had a mean number of courses of 4.9(R group,10.2) and mean survival time(MST) of 246 d(R group,402 d),showing that outcome was significantly better in R group(P=0.006).CONCLUSION:CE-US revealed that the change in intratumor blood flow correlated with both serum CA19-9 level and outcome.Patients with serum CA19-9 that decreased to less than half the baseline level,and patients with an abundant intratumor blood flow,had a significantly better outcome.Thus,CE-US is potentially useful for evaluating treatment efficacy and outcome in the early stages of pancreatic cancer chemotherapy.Atsushi Sofuni Takao Itoi Fumihide Itokawa Takayoshi Tsuchiya Toshio Kurihara Kentaro Ishii Syujiro Tsuji Nobuhito Ikeuchi Fuminori Moriyasu 2008World Journal of Gastroenterology2008,14,47:3
18Ganoderma lucidum spore oil(GLSO),a novel antioxidant,extends the average life span in Drosophila melanogaster显示文摘In ancient China,Ganoderma lucidum was believed to be a medical fungus that could increase lifespan.Recently,pharmacologic studies have found that polysaccharide peptides and triterpenoids extracted from Ganoderma lucidum have various physiological effects as active compounds.However,the effects of spore oil isolated from Ganoderma lucidum remains unknown.In this study,the biological effects of Ganoderma lucidum spore oil(GLSO)were evaluated using a Drosophila melanogaster model.Compared with untreated groups,groups treated with GLSO had significantly longer average and maximum lifespan in both normal conditions and under oxidative stress.The activities of various antioxidant enzymes were measured to determine the antioxidant effect of GLSO.GLSO treatment markedly enhanced total superoxide dismutase(SOD)and catalase(CAT)activity and decreased levels of malondialdehyde(MDA).Further,we found dose-dependent increases in the mRNA expression of Cu,Zn-SOD,Mn-SOD,and CAT in GLSO-treated groups.These results suggest that GLSO may effectively eliminate free radicals and extend lifespan in Drosophila.Future work should investigate the value of GLSO as a functional food for the prevention of aging in larger animal models.Yi Zhang Hongfei Cai Zhu Tao Cheng Yuan Zhaojian Jiang Juyan Liu Hiroshi Kurihara Wendong Xu 2021Food Science and Human Wellness2021,10,1:3
19A novel potent vasoconstrictor peptide produced by vascular endothelial cells显示文摘Yanagisawa M Kurihara H Kimura S 0,,6163:3
20The disbalance of LRP1 and SIRPα by psychological stress dampens the clearance of tumor cells by macrophages显示文摘The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies;however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stressevoked tumor susceptibility, and the stress hormone glucocorticoid(GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the 'eat me' signal receptor(low-density lipoprotein receptor-related protein-1, LRP1) and the 'don’t eat me' signal receptor(signal regulatory protein alpha, SIRPa). Further analysis revealed that GC led to a direct, glucocorticoid receptor(GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevatedgene level of SIRPa by down-regulating mi RNA-4695-3 p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPa axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPa axis may serve as a potential therapeutic strategy for tumor treatment.Yanping Wu Xiang Luo Qingqing Zhou Haibiao Gong Huaying Gao Tongzheng Liu Jiaxu Chen Lei Liang Hiroshi Kurihara Yi-Fang Li Rong-Rong He 2022Acta Pharmaceutica Sinica B2022,12,1:3
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