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Ulcerative colitis patients in clinical remission demonstrate correlations between fecal immunochemical test results, mucosal healing, and risk of relapse

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World Journal of Gastroenterology 2016年第21期22卷 5079-5087页

作者： Asuka Nakarai Jun Kato Sakiko Hiraoka Shiho Takashima Daisuke Takei Toshihiro Inokuchi Yuusaku Sugihara Masahiro Takahara Keita Harada Hiroyuki Okada Department of Gastroenterology and Hepatology Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Second Department of Internal medicine Wakayama Medical University Department of Endoscopy Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences

AIM: To assess the risk of relapse in ulcerative colitis (UC) patients in clinical remission using mucosal status and fecal immunochemical test (FIT) ***: The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores (MESs) and FIT ***: Patients with an MES of 0 (n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3 (n = 100, 52%) (HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result (fecal hemoglobin concentrations ≤ 100 ng/mL) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score (HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission > 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse (HR = 0.11, 95%CI: 0.04-0.23).CONCLUSION: Negative FIT results one year or more after remission induction correlate with complete mucosal healing (MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk.

关键词： Ulcerative colitis Clinical remission Mucosal healing Mayo endoscopic subscore Quantitative fecal immunochemical test

Circulating tumor DNA dynamics analysis in a xenograft mouse model with esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2021年第41期27卷 7134-7143页

作者： Hiroyuki Terasawa Hideaki Kinugasa Kazuhiro Nouso Shumpei Yamamoto Mami Hirai Takehiro Tanaka Akinobu Takaki Hiroyuki Okada Department of Gastroenterology and Hepatology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 7008558Japan Department of Pathology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 7008558Japan

BACKGROUND It remains unclear which factors,such as tumor volume and tumor invasion,influence circulating tumor DNA(ctDNA),and the origin of ctDNA in liquid biopsy is always *** use liquid biopsies clinically,it will be very important to address these *** To assess the origin of ctDNA,clarify the dynamics of ctDNA levels,assess ctDNA levels by using a xenograft mouse after treatment,and to determine whether tumor volume and invasion are related to ctDNA *** Tumor xenotransplants were established by inoculating BALB/c-nu/nu mice with the TE11 cell *** of mice were injected with xenografts at two or four sites and sacrificed at the appropriate time point after xenotransplantation for ctDNA *** of ctDNA was performed by droplet digital PCR,using the human telomerase reverse transcriptase(hTERT)*** Mice given two-site xenografts were sacrificed for ctDNA at week 4 and week *** hTERT was detected at week 4,but it was detected at week ***,in four-site xenograft mice,hTERT was detected both at week 4 and week *** experiments revealed that both tumor invasion and tumor volume were asso ciated with the detection of *** resection experiments,hTERT was detected at resection,but had decreased by 6 h,and was no longer detected 1 and 3 d after *** We clarified the origin and dynamics of ctDNA,showing that tumor volume is an important *** also found that when the tumor was completely resected,ctDNA was absent after one or more days.

关键词： Liquid biopsy Circulating tumor DNA Xenograft Esophageal squamous cell carcinoma Dynamics of circulating tumor DNA

Hernandezine promotes cancer cell apoptosis and disrupts the lysosomal acidic environment and cathepsin D maturation

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Chinese Journal of Natural medicines 2024年第5期22卷 387-401页

作者： FENG Qianwen SUN Lu Muhammad Jibran Sualeh ZHAO Qingli ZHAO Songji CUI Zhengguo INADERA Hidekuni Department of Public Health Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyama 930-8501Japan Department of Pediatric Cardiology Heart CenterGuangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510000China Department of Basic Medical sciences College of MedicineUniversity of SharjahSharjah 57545United Arab Emirates Department of Radiology Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyama 930-8501Japan Advanced Clinical Research Center Fukushima Global Medical Science CenterFukushima Medical UniversityFukushima CityFukushima 960-8074Japan Department of Environmental Health School of Medical SciencesUniversity of FukuiFukui 910-8580Japan

Hernandezine(Her),a bisbenzylisoquinoline alkaloid extracted from Thalictrum flavum,is recognized for its range of biological activities inherent to this herbal *** its notable properties,the anti-cancer effects of Her have remained largely *** this study,we elucidated that Her significantly induced cytotoxicity in cancer cells through the activation of apoptosis and necroptosis ***,Her triggered autophagosome formation by activating the AMPK and ATG5 conjugation systems,leading to LC3 *** findings revealed that Her caused damage to the mitochondrial membrane,with the damaged mitochondria undergoing mitophagy,as evidenced by the elevated expression of mitophagy ***,Her disrupted autophagic flux,demonstrated by the upregulation of p62 and accumulation of autolysosomes,as observed in the RFP-GFP-LC3 reporter ***,we determined that Her did not prevent the fusion of autophagosomes and ***,it inhibited the maturation of cathepsin D and increased lysosomal pH,indicating an impairment of lysosomal *** use of the early-stage autophagy inhibitor,3-methyladenine(3-MA),did not suppress LC3II,suggesting that Her also induces noncanonical autophagy in autophagosome *** application of Bafilomycin A1,an inhibitor of noncanonical autophagy,diminished the recruitment of ATG16L1 and the accumulation of LC3II by Her,thereby augmenting Her-induced cell *** observations imply that while autophagy initially plays a protective role,the disruption of the autophagic process by Her promotes programmed cell *** study provides the first evidence of Her’s dual role in inducing apoptosis and necroptosis while also initiating and subsequently impairing autophagy to promote apoptotic cell *** insights contribute to a deeper understanding of the mechanisms underlying programmed cell death,offering potential avenues for enhancing cancer prevention and therapeutic st

关键词： Hernandezine Apoptosis Mitophagy Autophagic flux Lysosome Noncanonical autophagy

Transient receptor potential vanilloid 4-dependent calcium influx and ATP release in mouse and rat gastric epithelia

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World Journal of Gastroenterology 2016年第24期22卷 5512-5519页

作者： Hiroshi Mihara Nobuhiro Suzuki Ammar Abdullkader Boudaka Jibran Sualeh Muhammad Makoto Tominaga Yoshiaki Tabuchi Toshiro Sugiyama Department of Gastroenterology Graduate School of Medicine and Pharmaceutical Sciences University of Toyama Division of Cell Signaling Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences) National Institutes of Natural Sciences Department of Physiology College of Medicine and Health Sciences Sultan Qaboos University Life Science Research Center University of Toyama

AIM: To explore the expression of transient receptor potential vanilloid 4(TRPV4) and its physiological meaning in mouse and rat gastric epithelia. METHODS: RT-PCR and immunochemistry were used to detect TRPV4 m RNA and protein expression in mouse stomach and a rat normal gastric epithelial cell line(RGE1-01), while Ca2+-imaging and electrophysiology were used to evaluate TRPV4 channel activity. ATP release was measured by a luciferin-luciferase assay. Gastric emptying was also compared between WT and TRPV4 knockout mice. RESULTS: TRPV4 m RNA and protein were detected in mouse tissues and RGE1-01 cells. A TRPV4-specific agonist(GSK1016790A) increased intracellular Ca2+ concentrations and/or evoked TRPV4-like current activities in WT mouse gastric epithelial cells andRGE1-01 cells, but not TRPV4 KO cells. GSK1016790 A or mechanical stimuli induced ATP release from RGE1-01 cells while TRPV4 knockout mice displayed delayed gastric emptying in vivo. CONCLUSION: TRPV4 is expressed in mouse and rat gastric epithelium and contributes to ATP release and gastric emptying.

关键词： Transient receptor potential vanilloid 4 Stomach gastric emptying ATP

Intussusception due to rectal adenocarcinoma in a young adult:A case report

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World Journal of Gastroenterology 2014年第35期20卷 12678-12681页

作者： Ryo Inada Takeshi Nagasaka Toshiaki Toshima Yoshiko Mori Yoshitaka Kondo Hiroyuki Kishimoto Toshiyoshi Fujiwara Department of Gastroenterological Surgery Okayama University Graduate School of MedicineDentistry and Pharmaceutical Sciences

An intussusception due to colonic adenocarcinoma has sometimes been reported. However, to the best of our knowledge, reports of intussusception due to rectal adenocarcinoma are extremely rare. In this report, the case of a young man with rectal adenocarcinoma causing intussusception is described. A 24-year-old man visited a hospital complaining of abdominal pain, and an upper rectal cancer was diagnosed by colonoscopy. Computed tomography showed intussusception caused by a large tumor in the pelvis and absence of distant metastases. Locally advanced rectal cancer causing intussusception was diagnosed, and a low anterior resection was performed. Intraoperatively, repair of the invagination could not be accomplished easily; therefore, the repair was abandoned. Instead, the tumor was removed en bloc to avoid dissemination of the cancer. Histopathologically, the tumor was diagnosed as a poorly differentiated adenocarcinoma, pStage IIA. The patient has no evidence of recurrence at 10 mo after the operation.

关键词： Adult intussusception En bloc resection Low anterior resection Rectal adenocarcinoma Young cancer

Fabrication of initial trabecular bone-inspired three-dimensional structure with cell membrane nano fragments

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Regenerative Biomaterials 2023年第1期10卷 73-80页

作者： Koichi Kadoya Emilio Satoshi Hara Masahiro Okada Yu Yang Jiao Takayoshi Nakano Akira Sasaki Takuya Matsumoto Department of Biomaterials Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 700-8558Japan Department of Maxillofacial Surgery Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 700-8558Japan Division of Materials&Manufacturing Science Osaka UniversityOsaka 565-0871Japan

The extracellular matrix of trabecular bone has a large surface exposed to the bone marrow and plays important roles such as hematopoietic stem cell niche formation and *** vitro reproduction of trabecular bone microenvironment would be valuable not only for developing a functional scaffold for bone marrow tissue engineering but also for understanding its biological ***,we analyzed and reproduced the initial stages of trabecular bone formation in mouse femur *** identified that the trabecular bone formation progressed through the following steps:(i)partial rupture of hypertrophic chondrocytes;(ii)calcospherite formation on cell membrane nano fragments(CNFs)derived from the ruptured cells;and(iii)calcospherite growth and fusion to form the initial three-dimensional(3D)structure of trabecular *** reproducing the initial trabecular bone formation in vitro,we collected CNFs from cultured cells and used as nucleation sites for biomimetic calcospherite ***,almost the same 3D structure of the initial trabecular bone could be obtained in vitro by using additional CNFs as a binder to fuse biomimetic calcospherites.

关键词： trabecular bone calcospherites cell membrane nano fragments three dimensionalization bone tissue synthesis

Hyperdry human amniotic membrane application as a wound dressing for a full-thickness skin excision after a third-degree burn injury

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Burns & Trauma 2020年第1期8卷 186-203页

作者： Jiro Oba Motonori Okabe Toshiko Yoshida Chika Soko Moustafa Fathy Koji Amano Daisuke Kobashi Masahiro Wakasugi Hiroshi Okudera Department of Emergency and Disaster medicine University of ToyamaToyama 930-0194Japan Department of Regenerative medicine Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyama 930-0194Japan Department of Biochemistry Faculty of PharmacyMinia UniversityMinia 61519Egypt Department of Emergency Surgery Sakai City Medical CenterSakaiOsaka 594-8304Japan

Background:Severe burn injuries create large skin defects that render the host susceptible to bacterial *** wound infection often causes systemic sepsis and severe septicemia,resulting in an increase in the mortality of patients with severe burn ***,appropriate wound care is important to prevent infection and improve patient ***,it is difficult to heal a third-degree burn *** aim of this studywas to investigate whether hyperdry human amniotic membrane(HD-AM)could promote early granulation tissue formation after full-thickness skin excision in third-degree burn injury sites in ***:After the development of HD-AM and creation of a third-degree burn injury model,the HD-AM was either placed or not placed on the wound area in the HD-AM group or HD-AM group,*** groups were prepared for evaluation on postoperative days 1,4 and *** staining was used for granulation tissue evaluation,and estimation of CD163,transforming growth factor beta-1(TGF-β1),vascular endothelial growth factor(VEGF),CD31,alpha-smooth muscle actin(α-SMA)and Iba1 expression was performed by immunohistochemical *** reverse-transcription polymerase chain reaction(PCR)was used to investigate gene expression of growth factors,cell migration chemokines and angiogenic and inflammatory ***:The HD-AM group showed significant early and qualitatively good growth of granulation tissue on the full-thickness skin excision ***-AM promoted early-phase inflammatory cell infiltration,fibroblast migration and angiogenesis in the granulation ***,the early infiltration of cells of the immune system was ***:HD-AM may be useful as a new wound dressing material for full-thickness skin excision sites after third-degree burn injuries,and may be a new therapeutic technique for improving the survival rate of patients with severe burn injuries.

关键词： Hyperdry human amniotic membrane Third-degree burn Granulation Cell migration Inflammation Angiogenesis

Edge and Core Impurity Transport Study With Spectroscopic Instruments in LHD

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Plasma Science and Technology 2009年第4期11卷 402-408页

作者： Shigeru MORITA Motoshi GOTO Masahiro KOBAYASHI Sadatsugu MUTO Malay Bikas CHOWDHURI 董春凤周航宇崔正英 Keisuke FUJII Akihiro FURUZAWA Masahiro HASUO AtsushiI WAMAE 揭银先 Mohammed KOUBITI Ikuya SAKURAI Yuzuru TAWARA 万宝年吴振伟 Naohiro YAMAGUCHI National Institute for Fusion Science Department of Fusion Science Graduate University for Advanced Studies Southwestern Institute of Physics Department of Engineering Physics Kyoto University EcoTopia Science Institute Nagoya University Institute of Plasma Physics Chinese Academy of Sciences PIIM University of Province Physics Laboratory Graduate School of Medicine and Pharmaceutical SciencesUniversity of Toyama

Impurity transport was investigated at both edge and core regions in large helical de- vice （LHD） with developed spectroscopic instruments which can measure one- and two-dimensional distributions of impurities. The edge impurity behavior was studied recently using four carbon resonant transitions in different ionization stages of CIII （977A）, CIV （1548A）, CV （40.3A） and CVI （33.7A）. When the line-averaged electron density, ne, is increased from 1 to 6 × 10^13 cm-3, the ratio of （CIII^CIV）/ne increases while the ratio of （CV＋CVI）/ne decreases. Here, CIII^CIV （CV＋CVI） expresses the sum of CIII （CV） and CIV （CVI） intensities. The CIII＋CIV indicates the carbon influx and the CV＋CVI indicates the emissions through the transport in the ergodic layer. The result thus gives experimental evidence on the impurity screening by the ergodic layer in LHD, which is also supported by a three-dimensional edge particle simulation. The core impu- rity behavior is also studied in high-density discharges （ne 〈 1 × 10^15 cm 3） with multi H2-pellets injection. It is found that the ratio of V/D （V： convection velocity, D： diffusion coefficient） decreases after pellet injection and Zeff profile shows a flat one at values of 1.1,-1.2. These results confirm no impurity accumulation occurs in high-density discharges. As a result, the iron density, rife, is analyzed to be 6 × 10^-7（=- nFe/ne） of which the amount can be negligible as radiation source even in such high-density discharges. One- and two-dimensional impurity distributions from space-resolved VUV and EUV spectrometers newly developed for further impurity transport study are also presented with their preliminary results.

关键词： impurity transport screening effect VUV spectroscopy

SRT1720, a SIRT1 Activator, Aggravates Bleomycin-Induced Lung Injury in Mice

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Food and Nutrition sciences 2012年第2期3卷 157-163页

作者： Shingo Imanishi Ryuji Hayashi Tomomi Ichikawa Kensuke Suzuki Masakiyo Sasahara Takashi Kondo Hirofumi Ogawa Kazuyuki Tobe Department of Pathology Graduate School of Medicine and Pharmaceutical Sciences University of Toyama Toyama Japan Department of Radiological sciences Graduate School of Medicine and Pharmaceutical Sciences University of Toyama Toyama Japan. First Department of Internal medicine Graduate School of Medicine and Pharmaceutical Sciences University of Toyama Toyama Japan

Diagnosis and management of interstitial lung diseases (ILDs), caused by lung epithelial injury followed by apoptosis, are often challenging. It has been controversial whether the SIRT1 protein, a principal modulator of longevity due to caloric restriction, ameliorates or aggravates ILD in animal models. Here we examined the effect of SRT1720, a syn- thetic activator of SIRT1, on bleomycin-induced lung injury in a mouse model and apoptosis in cultured epithelial cells. Oral intubation of SRT1720 over a period of 15 days caused body weight loss and a high mortality rate among bleomy- cin-treated mice. Histological examinations showed that the SRT1720 load increased fibrosis in the bleomycin-treated lung. An analysis of bronchoalveolar lavage fluid revealed remarkably increased numbers of inflammatory cells in the SRT1720-treated group. Moreover, the apoptosis of A549 lung cancer cells, caused by X-ray irradiation and an anti-Fas activating antibody, was promoted by SRT1720. These results indicate that SRT1720 not only aggravates bleomy- cin-induced ILD, but stimulates the apoptosis of physically and biologically stimulated A549 cells. While SIRT1 acti- vators are considered promising for the treatment of conditions such as diabetes mellitus, fatty liver, and chronic ob- structive pulmonary diseases, an excess of food containing SIRT1 activators may be harmful depending on the disease state, especially in the case of acute inflammation.

关键词： Interstitial Lung Diseases (ILDs) Lung Injury SIRT1 Bleomycin X-Ray Irradiation Oxidative Stress