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1Prognostic value of KRAS and BRAF mutations in curatively resected colorectal cancer显示文摘AIM: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability(MSI) status in Japanese colorectal cancer(CRC) population.METHODS: We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage Ⅰ-Ⅲ CRC and examined associations of these mutations with disease-free survival(DFS) and overall survival(OS) using uni- and multivariate Cox proportional hazards models.RESULTS: KRAS and BRAF mutations were detected in 312(38%) of 812 and 40(5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males(P = 0.02), while the presence of BRAF mutations was significantly associated with the female gender(P = 0.006), proximal tumor location(P < 0.001), mucinous or poorly differentiated histology(P < 0.001), and MSI-high tumors(P < 0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS(HR = 1.35; 95%CI: 1.03-1.75) and OS(HR = 1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS(HR = 2.20; 95%CI: 1.19-4.06) and OS(HR = 2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and OS.CONCLUSION: KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, inJapanese patients with curatively resected CRC.Shigenori Kadowaki Miho Kakuta Shuhei Takahashi Akemi Takahashi Yoshiko Arai Yoji Nishimura Toshimasa Yatsuoka Akira Ooki Kensei Yamaguchi Keitaro Matsuo Kei Muro Kiwamu Akagi 2015World Journal of Gastroenterology2015,21,4:14
2Nutritional status in relation to lifestyle in patients with compensated viral cirrhosis显示文摘AIM:To assess the nourishment status and lifestyle of non-hospitalized patients with compensated cirrhosis by using noninvasive methods.METHODS:The subjects for this study consisted of 27 healthy volunteers,59 patients with chronic viral hepatitis,and 74 patients with viral cirrhosis,from urban areas.We assessed the biochemical blood tests,anthropometric parameters,diet,lifestyle and physical activity of the patients.A homeostasis model assessment-insulin resistance(HOMA-IR) value of ≥ 2.5 was considered to indicate insulin resistance.We measured height,weight,waist circumference,arm circumference,triceps skin-fold thickness,and handgrip strength,and calculated body mass index,arm muscle circumference(AMC),and arm muscle area(AMA).We interviewed the subjects about their dietary habits and lifestyle using health assessment computer software.We surveyed daily physical activity using a pedometer.Univariate and multivariate logistic regression modeling were used to identify the relevant factors for insulin resistance.RESULTS:The rate of patients with HOMA-IR ≥ 2.5(which was considered to indicate insulin resistance) was 14(35.9%) in the chronic hepatitis and 17(37.8%) in the cirrhotic patients.AMC(%)(control vs chronic hepatitis,111.9% ± 10.5% vs 104.9% ± 10.7%,P = 0.021;control vs cirrhosis,111.9% ± 10.5% vs 102.7% ± 10.8%,P = 0.001) and AMA(%)(control vs chronic hepatitis,128.2% ± 25.1% vs 112.2% ± 22.9%,P = 0.013;control vs cirrhosis,128.2% ± 25.1% vs 107.5% ± 22.5%,P = 0.001) in patients with chronic hepatitis and liver cirrhosis were significantly lower than in the control subjects.Handgrip strength(%) in the cirrhosis group was significantly lower than in the controls(control vs cirrhosis,92.1% ± 16.2% vs 66.9% ± 17.6%,P < 0.001).The results might reflect a decrease in muscle mass.The total nutrition intake and amounts of carbohydrates,protein and fat were not significantly different amongst the groups.Physical activity levels(kcal/d)(control vs cirrhosis,210 ± 113 kcal/d vs 125 ± 74 kcal/d,P = 0.001),number of steps(step/d)(control vs cirrhosis,8070 ±3027 step/d vs 5789 ± 3368 step/d,P = 0.011),and exercise(Ex)(Ex/wk)(control vs cirrhosis,12.4 ± 9.3 Ex/wk vs 7.0 ± 7.7 Ex/wk,P = 0.013) in the cirrhosis group was significantly lower than the control group.The results indicate that the physical activity level of the chronic hepatitis and cirrhosis groups were low.Univariate and multivariate logistic regression modeling suggested that Ex was associated with insulin resistance(odds ratio,6.809;95% CI,1.288-36.001;P = 0.024).The results seem to point towards decreased physical activity being a relevant factor for insulin resistance.CONCLUSION:Non-hospitalized cirrhotic patients may need to maintain an adequate dietary intake and receive lifestyle guidance to increase their physical activity levels.Fumikazu Hayashi Chika Momoki Miho Yuikawa Yuko Simotani Etsushi Kawamura Atsushi Hagihara Hideki Fujii Sawako Kobayashi Shuji Iwai Hiroyasu Morikawa Masaru Enomoto Akihiro Tamori Norifumi Kawada Satoko Ohfuji Wakaba Fukusima Daiki Habu 2012World Journal of Gastroenterology2012,18,40:11
3Takotsubo cardiomyopathy: Pathophysiology,diagnosis and treatment显示文摘In 1990,takotsubo cardiomyopathy(TCM)was first discovered and reported by a Japanese cardiovascular specialist.Since then,this heart disease has gained worldwide acceptance as an independent disease entity.TCM is an important entity that differs from acute myocardial infarction.It occurs more often in postmenopausal elderly women,is characterized by a transient hypokinesis of the left ventricular(LV)apex,and is associated with emotional or physical stress.Wall motion abnormality of the LV apex is generally transient and resolves within a few days to several weeks.Its prognosis is generally good.However,there are some reports of serious TCM complications,including hypotension,heart failure,ventricular rupture,thrombosis involving the LV apex,and torsade de pointes.It has been suggested that coronary spasm,coronary microvascular dysfunction,catecholamine toxicity and myocarditis might contribute to the pathogenesis of TCM.However,its pathophysiology is not clearly understood.Kazuo Komamura Miho Fukui Toshihiro Iwasaku Shinichi Hirotani Tohru Masuyama 2014World Journal of Cardiology2014,6,7:9
4A new index for non-invasive assessment of liver fibrosis显示文摘AIM:To construct and evaluate a new non-invasive fibrosis index for assessment of the stage of liver f ibrosis. METHODS:A new f ibrosis index (Fibro-Stiffness index) was developed in 165 of 285 patients with chronic hepatitis C, and was validated in the other 120 patients where liver biopsy was performed. Its usefulness was compared with liver stiffness (LS) measured by FibroScan, the aminotransferase-to-platelet ratio index, the Forns index and the FibroIndex. RESULTS: The Fibro-Stiffness index consists of LS,platelet count and prothrombin time. The values of the Fibro-Stiffness index differed signif icantly between neighboring f ibrosis stages except F0-F1. The area under the receiver operating characteristics curves of the Fibro-Stiffness index for prediction of F≥2 (0.90), F≥ 3 (0.90) and F= 4(0.92) in the estimation group and those for F≥ 3 (0.93) and F =4 (0.97) in the validation group were the highest among the 5 methods examined. The accuracy of the Fibro-Stiffness index had highest values for F≥2, F≥3 and F=4 in both the estimation and validation groups. The diagnostic performance for F= 4 was improved by a combination of the Fibro-Stiffness index with serum hyaluronic acid level. CONCLUSION: The Fibro-Stiffness index was constructed and validated. It showed superior diagnostic performance to other indices for F ≥ 2,3 and 4.Naohiro Ichino Keisuke Osakabe Toru Nishikawa Hiroko Sugiyama Miho Kato Shiho Kitahara Senju Hashimoto Naoto Kawabe Masao Harata Yoshifumi Nitta Michihito Murao Takuji Nakano Yuko Arima Hiroaki Shimazaki Koji Suzuki Kentaro Yoshioka 2010World Journal of Gastroenterology2010,16,38:7
5The increase in surface CXCR4 expression on lung extravascular neutrophils and its effects on neutrophils during endotoxin-induced lung injury显示文摘Inflammatory stimuli,such as a microbes or lipopolysaccharides,induce a rapid release of neutrophils from the bone marrow and promote neutrophil migration into inflamed sites to promote host defense.However,an excess accumulation and retention of neutrophils in inflamed tissue can cause severe tissue injuries in the later stages of inflammation.Recent studies have reported that both CXCL12 levels in injured lungs and its receptor,CXCR4,on accumulated neutrophils in injured lungs,increased;furthermore,these studies showed that the CXCL12/CXCR4 signaling pathway participated in neutrophil accumulation in the later stages of lipopolysaccharide(LPS)-induced lung injury.However,the mechanisms underlying this increase in surface CXCR4 expression in neutrophils remain unclear.In this study,we found that surface CXCR4 expression increased in extravascular,but not intravascular,neutrophils in the lungs of LPS-induced lung injury model mice.Furthermore,ex vivo studies revealed that CXCL12 acted not only as a chemoattractant,but also as a suppressor of cell death for the lung neutrophils expressing CXCR4.Sulfatide,one of the native ligands for L-selectin,induced the increase of surface CXCR4 expression on isolated circulating neutrophils,suggesting that the activation of L-selectin may be involved in the increase in surface CXCR4.Our findings show that surface CXCR4 levels on neutrophils increase after extravasation into injured lungs,possibly through the activation of L-selectin.The CXCL12/CXCR4 signaling pathway plays an important role in the modulation of neutrophil activity during acute lung injury,not only by promoting chemotaxis but also by suppressing cell death.Mitsuhiro Yamada Hiroshi Kubo Seiichi Kobayashi Kota Ishizawa Mei He Takaya Suzuki Naoya Fujino Hiroyuki Kunishima Masamitsu Hatta Katsushi Nishimaki Tetsuji Aoyagi Kouichi Tokuda Miho Kitagawa Hisakazu Yano Hirokazu Tamamura Nobutaka Fujii Mitsuo Kaku 2011Cellular & Molecular Immunology2011,8,4:6
6Colon perforation due to antigenemia-negative cytomegalovirus gastroenteritis after liver transplantation: A case report and review of literature显示文摘BACKGROUND Cytomegalovirus(CMV) remains a critical complication after solid-organ transplantation. The CMV antigenemia(AG) test is useful for monitoring CMV infection. Although the AG-positivity rate in CMV gastroenteritis is known to be low at onset, almost all cases become positive during the disease course. We treated a patient with transverse colon perforation due to AG-negative CMV gastroenteritis, following a living donor liver transplantation(LDLT).CASE SUMMARY The patient was a 52-year-old woman with decompensated liver cirrhosis as a result of autoimmune hepatitis who underwent a blood-type compatible LDLT with her second son as the donor. On day 20 after surgery, upper and lower gastrointestinal endoscopy(GE) revealed multiple gastric ulcers and transverse colon ulcers. The biopsy tissue immunostaining confirmed a diagnosis of CMV gastroenteritis. On day 28 after surgery, an abdominal computed tomography revealed transverse colon perforation, and simple lavage and drainage were performed along with an urgent ileostomy. Although the repeated remission and aggravation of CMV gastroenteritis and acute cellular rejection made the control of immunosuppression difficult, the upper GE eventually revealed an improvement in the gastric ulcers, and the biopsy samples were negative for CMV. The CMV-AG test remained negative, therefore, we had to evaluate the status of the CMV infection on the basis of the clinical symptoms and GE.CONCLUSION This case report suggests a monitoring method that could be useful for AGnegative CMV gastroenteritis after a solid-organ transplantation.Takahiro Yokose Hideaki Obara Masahiro Shinoda Yutaka Nakano Minoru Kitago Hiroshi Yagi Yuta Abe Yohei Yamada Kentaro Matsubara Go Oshima Shutaro Hori Sho Ibuki Hisanobu Higashi Yuki Masuda Masanori Hayashi Miho Kawaida Takehiko Mori Takumi Fujimura Ken Hoshino Kaori Kameyama Tatsuo Kuroda Yuko Kitagawa 2019World Journal of Gastroenterology2019,25,15:5
7Decrease in Serum Amyloid a Protein Levels Following Three-month Stays in Negatively Charged Particle-dominant Indoor Air Conditions显示文摘Objective The changes in serum adipokines and cytokines related to oxidative stress were examined during 3 months ‘Off to On' and ‘On to Off' periods using negatively charged particle-dominant indoor air conditions(NCPDIAC).Methods Seven volunteers participated in the study,which included ‘OFF to 3 months ON' periods(ON trials) for a total of 16 times,and ‘ON to 3 months OFF'(OFF trials) periods for a total of 13 times.Results With the exception of one case,serum amyloid A(SAA) levels decreased significantly during the ON trials.Conclusion Considering that SAA is an acute phase reactive protein such as C reactive protein(CRP),this observed decrease might indicate the prevention of cardiovascular and atherosclerotic changes,since an increase in high-sensitive CRP is associated with the subsequent detection of these events.Suni Lee Shoko Yamamoto Yasumitsu Nishimura Hidenori Matsuzaki Kei Yoshitome Tamayo Hatayama Miho Ikeda YU Min Nagisa Sada Naoko Kumagai-Takei Takemi Otsuki 2018Biomedical and Environmental Sciences2018,31,5:5
8中印传统医药合作推进行动的政策建议显示文摘本文针对以西药为基础的发展中国家医疗保健高费用问题,提出建立'中印传统医药合作推进行动',借鉴健康影响基金的机制,通过中印两国在传统医药研究开发、质量控制、标准化、临床试验、监管体系、知识产权保护等方面的合作,探索面向低收入人群的、以传统医药为基础的医药创新、知识产权保护与医疗保健服务模式。Sachin Chaturvedi 高志前 Mihos ladikas Thomas pogge 2011中国科技论坛2011,,4:5
9Effect of herbal medicine Juzentaihoto on hepatic and intestinal heat shock gene expression requires intestinal microflora in mouse显示文摘AIM: To evaluate the role of intestinal microflora in the effects of multi-herbal medicine on gene expression in the gut and liver. METHODS: The multi-herbal medicine Juzentaihoto (JTX) was administered to five germ-free mice and regular mice for 2 wk. Among the results of the comprehensive gene chip analysis of the intestine and liver, we featured heat shock proteins (HSPs) 70 and 105 because their gene expression changed only in the presence of microflora. Real-time RT-PCR was performed to confirm the expression levels of these HSP genes. To determine whether JTX acts directly on the HSP genes, sodium arsenite (SA) was used to induce the heat shock proteins directly. To examine the change of the intestinal microflora with administration of JTX, the terminal restriction fragment polymorphism (T-RFLP) method was used. To identify the changed bacteria, DNA sequencing was performed. RESULTS: Heat shock protein gene expression,documented by gene chip and real-time RT-PCR, changed with the administration of JTX in the regular mice but not in the germ-free mice. JTX did not suppress the direct induction of the HSPs by SA. T-RFLP suggested that JTX decreased unculturable bacteria and increased Lactobacillus johnsoni. These data suggested that JTX changed the intestinal microflora which, in turn, changed HSP gene expression. CONCLUSION: Intestinal microflora affects multi-herbal product JTX on the gene expression in the gut and liver.Miho Kato Atsushi Ishige Naoko Anjiki Masahiro Yamamoto Yoshifumi Irie Mitsue Taniyama Ryoko Kibe Junichiro Oka Yoshimi Benno Kenji Watanabe 2007World Journal of Gastroenterology2007,13,16:5
10RANKL-RANK interaction in immune regulatory systems显示文摘The interaction between the receptor activator of NF-κB ligand(RANKL)and its receptor RANK plays a critical role in the development and function of diverse tissues.This review summarizes the studies regarding the functions of RANKL signaling in immune regulatory systems.Previous in vitro and in vivo studies have indicated that the RANKL signal promotes the survival of dendritic cells(DCs),thereby activating the immune response.In addition,RANKL signaling to DCs in the body surface barriers controls self-tolerance and oral-tolerance through regulatory T cell functions.In addition to regulating DC functions,the RANKL and RANK interaction is critical for the development and organization of several lymphoid organs.The RANKL signal initiates the formation of clusters of lymphoid tissue inducer cells,which is crucial for lymph node organogenesis.Moreover,the RANKL-RANK interaction controls the differentiation of M cells,specialized epithelial cells in mucosal tissues,that take up and transcytose antigen particles to control the immune response to pathogens or commensal bacterium.The development of epithelial cells localized in the thymic medulla(m TECs)is also regulated by the RANKL-RANK signal.Given that the unique property ofm TECs to express a wide variety of tissue-specific selfantigens is critical for the elimination of self-antigen reactive T cells in the thymus,the RANKL-RANK interaction contributes to the suppression of autoimmunity.Future studies on the roles of the RANKL-RANK system in immune regulatory functions would be informative for the development and application of inhibitors of RANKL signaling for disease treatment.Taishin Akiyama Miho Shinzawa Nobuko Akiyama 2012World Journal of Orthopedics2012,3,9:5
11A comparative study on crash-influencing factors by facility types on urban expressway显示文摘This study aims at identifying crash-influencing factors by facility type of Nagoya Urban Expressway,considering the interaction of geometry,traffic flow,and ambient conditions.Crash rate(CR)model is firstly developed separately at four facility types:basic,merge,and diverge segments and sharp curve.Traffic flows are thereby categorized,and based on the traffic categories,the significances of factors affecting crashes are analyzed by principal component analysis.The results reveal that,die CR at merge segment is significantly higher than those at basic and diverge segments in uncongested flow,while the value is not significantly different at the three facility types in congested flow.In both un-and congested flows,sharp curve has the worst safety performance in view of its highest CR.Regarding influencing factors,geometric design and traffic flow are most significant in un-and congested flows,respectively.As mainline flow increases,the effect of merging ratio affecting crash is on the rise at basic and merge segments as opposed to the decreasing significance of diverging ratio at diverge segment.Meanwhile,longer acceleration and deceleration lanes are adverse to safety in uncongested flow,while shorter acceleration and deceleration lanes are adverse in congested flow.Due to its special geometric design,crashes at sharp curve are highly associated with the large centrifugal force and heavy restricted visibility.Yong Wu Hideki Nakamura Miho Asano 2013Journal of Modern Transportation2013,21,4:4
12Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virusinfected liver显示文摘AIM:To investigate the relationship between the ironmetabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C patients.METHODS:The hepatic expression profile of ironmetabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated.A hundred patients with chronic hepatitis C(genotype1b,n = 50; genotype 2,n = 50) were enrolled and retrospectively analyzed.Liver biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolismrelated genes and protein expression(Western blotting analysis) for ferroportin.As a control,normal liver tissue was obtained from 18 living donors of liver transplantation.Serum hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass spectrometry.RESULTS:Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus(HCV)is reported to induce iron accumulation in hepatocytes in vivo.Conversely,iron administration suppresses HCV replication in vitro.Therefore,the association between HCV infection and iron metabolism remains unclear.Compared with controls,patients had significantly higher gene expression for transferrin,iron-regulatoryproteins 1 and 2,divalent metal transporter 1,and ferroportin,but similar for transferrin receptors 1 and2,and hepcidin.When the expression profiles were compared between sustained virological response(SVR)and non-SVR patients,the former showed significantly lower transcription and protein expression of hepcidin and ferroportin.Expression of hepcidin-regulating genes,BMPR1,BMPR2,and hemojuvelin,was significantly increased,whereas BMP2 was decreased in HCV-infected liver.BMPR2 and hemojuvelin expression was significantly lower in the SVR than non-SVR group.HCV infection affects the expression of iron-metabolism-related genes,leading to iron accumulation in hepatocytes.CONCLUSION:Decreased expression of hepcidin and ferroportin in SVR patients indicates the importance of hepatocytic iron retention for viral response during pegylated-interferon plus ribavirin treatment.Motoyuki Kohjima Tsuyoshi Yoshimoto Munechika Enjoji Nobuyoshi Fukushima Kunitaka Fukuizumi Tsukasa Nakamura Miho Kurokawa Nao Fujimori Yusuke Sasaki Yasushi Shimonaka Yusuke Murata Susumu Koyama Ken Kawabe Kazuhiro Haraguchi Yorinobu Sumida Naohiko Harada Masaki Kato Kazuhiro Kotoh Makoto Nakamuta 2015World Journal of Gastroenterology2015,21,11:4
13Evaluation of effects of a novel endoscopically applied radiofrequency ablation biliary catheter using an ex-vivo pig liver显示文摘Takao Itoi Hiroyuki Isayama Atsushi Sofuni Fumihide Itokawa Miho Tamura Yusuke Watanabe Fuminori Moriyasu Michel Kahaleh Nagy Habib Toshitaka Nagao Tomohisa Yokoyama Kazuhiko Kasuya Hiroshi Kawakami 2012Journal of Hepato-Biliary-Pancreatic Sciences2012,,5:3
14A case of hemangiopericytoma of the soft palate with articulate disorder and dysphagia显示文摘We report a case of hemangiopericytoma of the soft palate of 60-year-old patient, who noticed a mass of the soft palate and experienced difficulty in speaking. We found a pediculate, hard, elastic mass measuring 38 mm (cross-sectional diameter). Computed tomography (CT) scans and dynamic magnetic resonance imaging (MRI) confirmed irregularly shaped mass and revealed a heterogeneous internal composition, consistent with vascular tumors. We excised the tumor under general anesthesia. Histopathological diagnosis was based on positive immunoreactivity of CD99 and vimentin and weak, positive staining of CD34. Three and half years following tumor excision, there is no recurrence or metastasis.Yasuyuki Michi Miho Suzuki Kazuto Kurohara Kiyoshi Harada 2013International Journal of Oral Science2013,5,2:3
15Dephosphorylation of Translation Initiation Factor 2α Enhances Glucose Tolerance and Attenuates Hepatosteatosis in Mice显示文摘Seiichi Oyadomari Heather P. Harding Yuhong Zhang Miho Oyadomari David Ron 2008Cell Metabolism2008,,6:2
16JPN Guidelines for the management of acute pancreatitis: epidemiology, etiology, natural history, and outcome predictors in acute pancreatitis显示文摘Miho Sekimoto Tadahiro Takada Yoshifumi Kawarada Koichi Hirata Toshihiko Mayumi Masahiro Yoshida Masahiko Hirota Yasutoshi Kimura Kazunori Takeda Shuji Isaji Masaru Koizumi Makoto Otsuki Seiki Matsuno 2006Journal of Hepato-Biliary-Pancreatic Surgery2006,,:2
17JPN Guidelines for the management of acute pancreatitis: epidemiology, etiology, natural history, and outcome predictors in acute pancreatitis显示文摘Miho Sekimoto Tadahiro Takada Yoshifumi Kawarada Koichi Hirata Toshihiko Mayumi Masahiro Yoshida Masahiko Hirota Yasutoshi Kimura Kazunori Takeda Shuji Isaji Masaru Koizumi Makoto Otsuki Seiki Matsuno 2006Journal of Hepato - Biliary - Pancreatic Surgery2006,,1:2
18Hepatocarcinogenesis in chronic hepatitis C patients achieving a sustained virological response to interferon: significance of lifelong periodic cancer screening for improving outcomes显示文摘Naoki Yamashita Aritsune Ohho Akihiro Yamasaki Miho Kurokawa Kazuhiro Kotoh Eiji Kajiwara 2014Journal of Gastroenterology2014,,11:2
19Low temperature surface oxygen activation in crystalline MnO_(2) triggered by lattice confined Pd single atoms显示文摘Tuning the coordination environment is the research axis of single atom catalysts (SACs). SACs are commonly stabilized by various defects from support. Here, we report a lattice confined Pd SAC using MnO_(2) as support. Compared with the Pd clusters anchored on the surface, the lattice confined Pd single atoms allows spontaneous exaction of surrounding lattice oxygen at room temperature when employed in CO oxidation. The MnO_(2) supported Pd SAC exhibited a high turnover frequency of 0.203 s^(−1) at low reaction temperature, which is higher than that of recently reported Pd SACs. Theoretical calculations also confirmed the confined monatomic Pd activate lattice oxygen with an ultralow energy barrier. Our results illustrate that the unique coordination environment of single atom provided by lattice confinement is promising to boost the activity of SACs.Xuemei Liao Yonghui Zhao Changwen Liu Xiaopeng Li Yu Sund Kenichi Kato Miho Yamauchi Zheng Jiang 2021Journal of Energy Chemistry2021,30,11:2
20Daikenchuto (Da-Jian-Zhong-Tang) ameliorates intestinal fibrosis by activating myofibroblast transient receptor potential ankyrin 1 channel显示文摘AIM To investigate the anti-fibrotic effects of the traditional oriental herbal medicine Daikenchuto(DKT) associated with transient receptor potential ankyrin 1(TRPA1) channels in intestinal myofibroblasts. METHODS Inflammatory and fibrotic changes were detected in a2,4,6-trinitrobenzenesulfonic acid(TNBS) chronic colitis model of wild-type and TRPA1-knockout(TRPA1-KO) mice via pathological staining and immunoblotting analysis.Ca^(2+) imaging experiments examined the effects of DKT and its components/ingredients on intestinal myofibroblast(In Myo Fib) cell TRPA1 channel function.Profibrotic factors and transforming growth factor (TGF) -β1-associated signaling were tested in an In Myo Fib cell line by q PCR and immunoblotting experiments.Samples from non-stenotic and stenotic regions of the intestines of patients with Crohn’s disease (CD) were used for pathological analysis. RESULTS Chronic treatment with TNBS caused more severe inflammation and fibrotic changes in TRPA1-KO than in wild-type mice.A one-week enema administration of DKT reduced fibrotic lesions in wild-type but not in TRPA1-KO mice.The active ingredients of DKT,i.e.,hydroxyα-sanshool and 6-shogaol,induced Ca^(2+) influxes in In Myo Fib,and this was antagonized by co-treatment with a selective TRPA1 channel blocker,HC-030031.DKT counteracted TGF-β1-induced expression of TypeⅠcollagen andα-smooth muscle actin (α-SMA) ,which were accompanied by a reduction in the phosphorylation of Smad-2 and p38-mitogen-activated protein kinase (p38-MAPK) and the expression of myocardin.Importantly,24-h incubation with a DKT active component Japanese Pepper increased the m RNA and protein expression levels of TRPA1 in In Myo Fibs,which in turn negatively regulated collagen synthesis.In the stenotic regions of the intestines of CD patients,TRPA1 expression was significantly enhanced.CONCLUSION The effects of DKT on the expression and activation of the TRPA1 channel could be advantageous for suppressing intestinal fibrosis,and benefit inflammatory bowel disease treatment.Keizo Hiraishi Lin-Hai Kurahara Miho Sumiyoshi Yao-Peng Hu Kaori Koga Miki Onitsuka Daibo Kojima Lixia Yue Hidetoshi Takedatsu Yu-Wen Jian Ryuji Inoue 2018World Journal of Gastroenterology2018,24,35:2
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