Inflammation in gastric cancer: Interplay of the COX-2/prostaglandin E2 and Toll-like receptor/MyD88 pathways

Cyclooxygenase-2 (COX-2) and its downstream product prostaglandin E2 (PGE2) play a key role in generation of the inflammatory microenvironment in tumor tissues. Gastric cancer is closely associated with Helicobacter pylori infection, which stimulates innate immune responses through Toll-like receptors (TLRs), inducing COX-2/PGE2 pathway through nuclear factor-κB activation. A pathway analysis of human gastric cancer shows that both the COX-2 pathway and Wnt/β-catenin signaling are significantly activated in tubular-type gastric cancer, and basal levels of these pathways are also increased in other types of gastric cancer. Expression of interleukin-11, chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2, and CXCL5, which play tumor-promoting roles through a variety of mechanisms, is induced in a COX-2/PGE2 pathway-dependent manner in both human and mouse gastric tumors. Moreover, the COX-2/PGE2 pathway plays an important role in the maintenance of stemness with expression of stem cell markers, including CD44, Prom1, and Sox9, which are induced in both gastritis and gastric tumors through a COX-2/PGE2-dependent mechanism. In contrast, disruption of Myd88 results in suppression of the inflammatory microenvironment in gastric tumors even when the COX-2/PGE2 pathway is activated, indicating that the interplay of the COX-2/PGE2 and TLR/MyD88 pathways is needed for inflammatory response in tumor tissues. Furthermore, TLR2/MyD88 signaling plays a role in maintenance of stemness in normal stem cells as well as gastric tumor cells. Accordingly, these results suggest that targeting the COX-2/PGE2 pathway together with TLR/MyD88 signaling, which would suppress the inflammatory microenvironment and maintenance of stemness, could be an effective preventive or therapeutic strategy for gastric cancer. © 2016 Japanese Cancer Association

Fluid-Structure Interaction Analysis for Martian Exploration Parafoil with Deployable Structure by Coupling Library Precice

trigger aerodynamic instability. Although instability has been reported in wind tunnel experiments and flight tests, the detailed mechanism of this possible instability has not been clarified. Therefore, it is necessary to elucidate the detailed instability mechanism by numerical analysis, as it cannot be realized experimentally. In addition, it is necessary to introduce fluid-structure interaction (FSI) analysis for flexible structures using a coupled method. The precise code interaction coupling environment (preCICE) coupling library is a powerful tool for the coupling analysis of fluid and structure solvers.  To evaluate the effect of coupling two physical fields, the analyses of the fluid and structure were conducted separately. The results of the analysis verified that the wing deformed under a fluid force, which indicates the effectiveness of the FSI analysis model developed. A comparison with the single-field analysis demonstrated that the structure-derived frequencies in the FSI analysis appeared in the wing surface deformation and aerodynamic forces. However, the aerodynamic coefficients obtained by the FSI analysis converged to the same values as those obtained by the single fluid analysis, thus indicating that from a macroscopic perspective, structural deformation negligibly influences aerodynamic forces. Therefore, it is necessary to analyze a shape that is closer to the actual machine

Brain MRI with Quantitative Susceptibility Mapping: Relationship to CT Attenuation Values

[Background]: Quantitative susceptibility mapping (QSM) is used to differentiate between calcification and iron deposits. Few studies have examined the relationship between CT attenuation values and magnetic susceptibility in such materials. Purpose: To assess the relationship among metal concentration, CT attenuation values, and magnetic susceptibility in paramagnetic and diamagnetic phantoms, and the relationship between CT attenuation values and susceptibility in brain structures that have paramagnetic or diamagnetic properties. [Materials and Methods]: In this retrospective study, CT and MRI with QSM were performed in gadolinium and calcium phantoms, patients, and healthy volunteers between June 2016 and September 2017. In the phantom study, we evaluated correlations among metal concentration, CT attenuation values, and susceptibility. In the human study, Pearson and Spearman correlations were performed to assess the relationship between CT attenuation values and susceptibility in regions of interest placed in the globus pallidus (GP), putamen, caudate nucleus, substantia nigra, red nucleus, dentate nucleus, choroid plexus, and hemorrhagic and calcified lesions. [Results]: Eighty-four patients (mean age, 64.8 years 6 19.6; 49 women) and 20 healthy volunteers (mean age, 72.0 years 6 7.6; 11 men) were evaluated. In the phantoms, strong linear correlations were identified between gadolinium concentration and CT and MRI QSM values (R2 = 0.95 and 0.99, respectively; P , .001 for both) and between calcium concentration and CT and MRI QSM values (R2 = 0.89 [P = .005] and R2 = 0.98 [P , .001], respectively). In human studies, positive correlations between CT attenuation values and susceptibility were observed in the GP (R2 = 0.52, P , .001) and in hemorrhagic lesions (R2 = 0.38, P , .001), and negative correlations were found in the choroid plexus (R2 = 0.53, P , .001) and in calcified lesions (R2 = 0.38, P = .009). [Conclusion]: CT attenuation values showed a positive correlation with susceptibility in the globus pallidus and hemorrhagic lesions and negative correlation in the choroid plexus and calcified lesions

Epitaxially Stabilized EuMoO3: A New Itinerant Ferromagnet

Synthesizing metastable phase often opens new functions in materials but is a challenging topic. Thin film techniques have advantages to form materials which do not exist in nature since nonequilibrium processes are frequently utilized. In this study, we successfully synthesize epitaxially stabilized new compound of perovskite Eu2+Mo4+O3 as a thin film form by a pulsed laser deposition. Analogous perovskite SrMoO3 is a highly conducting paramagnetic material, but Eu2+ and Mo4+ are not compatible in equilibrium and previous study found more stable pyrochlore Eu23+Mo24+O7 prefers to form. By using isostructural perovskite substrates, the gain of the interface energy between the film and the substrate stabilizes the matastable EuMoO3 phase. This compound exhibits high conductivity and large magnetic moment, originating from Mo 4d2 electrons and Eu 4f7 electrons, respectively. Our result indi-cates the epitaxial stabilization is effective not only to stabilize crystallographic structures but also to from a new compound which contains unstable combinations of ionic valences in bulk form.Comment: 7 pages, 9 figure

Neuromelanin‐Sensitive Magnetic Resonance Imaging Using DANTE Pulse

BACKGROUND: Neuromelanin-sensitive magnetic resonance imaging techniques have been developed but currently require relatively long scan times. The aim of this study was to assess the ability of black-blood delay alternating with nutation for tailored excitation-prepared T1-weighted variable flip angle turbo spin echo (DANTE T1-SPACE), which provides relatively high resolution with a short scan time, to visualize neuromelanin in the substantia nigra pars compacta (SNpc). METHODS: Participants comprised 49 healthy controls and 25 patients with Parkinson's disease (PD). Contrast ratios of SNpc and hyperintense SNpc areas, which show pixels brighter than thresholds, were assessed between DANTE T1-SPACE and T1-SPACE in healthy controls. To evaluate the diagnostic ability of DANTE T1-SPACE, the contrast ratios and hyperintense areas were compared between healthy and PD groups, and receiver operating characteristic analyses were performed. We also compared areas under the curve (AUCs) between DANTE T1-SPACE and the previously reported gradient echo neuromelanin (GRE-NM) imaging. Each analysis was performed using original images in native space and images transformed into Montreal Neurological Institute space. Values of P < 0.05 were considered significant. RESULTS: DANTE T1-SPACE showed significantly higher contrast ratios and larger hyperintense areas than T1-SPACE. On DANTE T1-SPACE, healthy controls showed significantly higher contrast ratios and larger hyperintense areas than patients with PD. Hyperintense areas in native space analysis achieved the best AUC (0.94). DANTE T1-SPACE showed AUCs as high as those of GRE-NM. CONCLUSIONS: DANTE T1-SPACE successfully visualized neuromelanin of the SNpc and showed potential for evaluating PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Two-Minute Quantitative Susceptibility Mapping From Three-Dimensional Echo-Planar Imaging: Accuracy, Reliability, and Detection Performance in Patients With Cerebral Microbleeds

Objectives: The aim of this study was to assess the accuracy, reliability, and cerebral microbleed (CMB) detection performance of 2-minute quantitative susceptibility mapping (QSM) from 3-dimensional echo-planar imaging (3D-EPI). Materials and Methods: Gadolinium phantom study was conducted using 3D-EPI, single–echo time (TE), and multi-TE gradient-recalled echo (GRE) sequences on two 3-T magnetic resonance (MR) scanners to assess the accuracy between measured and theoretical susceptibility values. The institutional review board approved this prospective study, and 40 healthy volunteers were enrolled with written consent between April 2018 and October 2019. Each underwent 3D-EPI, single-TE, and multi-TE GRE sequences consecutively on one 3-T MR scanner, and QSMs were calculated to assess the reliability of 3D-EPI QSM. Intraclass correlation coefficient (ICC), linear regression, and Bland-Altman plots were calculated. Patients with CMB who underwent both 3D-EPI and GRE QSM scans were retrospectively enrolled. Two radiologists evaluated images independently, and Cohen κ coefficients were calculated to compare CMB detection performance. Results: Phantom study showed excellent validity of 3D-EPI QSM on both MR scanners: Skyra, R2 = 0.996, P < 0.001, ICC = 0.997, mean difference, −2 ppb (95% confidence interval [CI], −45 to 40 ppb); Prisma, R2 = 0.992, P < 0.001, ICC = 0.988, mean difference, 15 ppb (95% CI, −67 to 97 ppb). A human study of 40 healthy volunteers (59 ± 13 years, 25 women) showed excellent reliability with 3D-EPI QSM for both single-TE and multi-TE GRE (R2 = 0.981, P < 0.001, ICC = 0.988; R2 = 0.983, P < 0.001, ICC = 0.990, respectively), supported by a Bland-Altman mean difference of 4 ppb (95% CI, −15 to 23 ppb) for single-TE GRE and 3 ppb (95% CI, −15 to 20 ppb) for multi-TE GRE. The CMB detection performance evaluation from 38 patients (51 ± 20 years, 20 women) showed almost perfect agreement between 3D-EPI and GRE QSM for both raters (κ = 0.923 and 0.942, P < 0.001). Conclusions: Faster QSM from 3D-EPI demonstrated excellent accuracy, reliability, and CMB detection performance

Three-dimensional Structure of Nylon Hydrolase and Mechanism of Nylon-6 Hydrolysis

This research was originally published in the Journal of Biological Chemistry. Seiji Negoro, Naoki Shibata, Yusuke Tanaka, Kengo Yasuhira, Hiroshi Shibata, Haruka Hashimoto, Young-Ho Lee, Shohei Oshima, Ryuji Santa, Shohei Oshima, Kozo Mochiji, Yuji Goto, Takahisa Ikegami, Keisuke Nagai, Dai-ichiro Kato, Masahiro Takeo and Yoshiki Higuchi. Three-dimensional Structure of Nylon Hydrolase and Mechanism of Nylon-6 Hydrolysis. J. Biol. Chem. 2012; 287, 5079-5090. © the American Society for Biochemistry and Molecular Biolog

2015年「みらい」北極航海における海洋観測

MR15-03講演要旨 / ブルーアース2016（2016年3月8日～9日, 東京海洋大学品川キャンパス）http://www.godac.jamstec.go.jp/darwin/cruise/mirai/mr15-03/

Quiet Diffusion-weighted MR Imaging of the Brain for Pediatric Patients with Moyamoya Disease

PURPOSE: Diffusion-weighted MRI (DWI) is an essential sequence for evaluating pediatric patients with moyamoya disease (MMD); however, acoustic noise associated with DWI may lead to motion artifact. Compared with conventional DWI (cDWI), quiet DWI (qDWI) is considered less noisy and able to keep children more relaxed and stable. This study aimed to evaluate the suitability of qDWI compared with cDWI for pediatric patients with MMD. METHODS: In this observational study, MR examinations of the brain were performed either with or without sedation in pediatric patients with MMD between September 2017 and August 2018. Three neuroradiologists independently evaluated the images for artifacts and restricted diffusion in the brain. The differences between qDWI and cDWI were compared statistically using a chi-square test. RESULTS: One-hundred and six MR scans of 56 patients with MMD (38 scans of 15 sedated patients: 6 boys and 9 girls; mean age, 5.2 years; range, 1-9 years; and 68 scans of 42 unsedated patients: 19 boys and 23 girls; mean age, 10.7 years; range, 7-16 years) were evaluated. MR examinations were performed either with or without sedation (except in one patient). In sedated patients, no artifact other than susceptibility was observed on qDWI, whereas four artifacts were observed on cDWI (P = .04). One patient awoke from sedation during cDWI scanning, while no patient awoke from sedation during qDWI acquisition. For unsedated patients, three scans showed artifacts on qDWI, whereas two scans showed artifacts on cDWI (P = .65). Regarding restricted diffusion, qDWI revealed three cases, while two cases were found on cDWI (P = .66). CONCLUSION: qDWI induced fewer artifacts compared with cDWI in sedated patients, and similar frequencies of artifacts were induced by qDWI and by cDWI in unsedated patients. qDWI showed restricted diffusion comparable to cDWI