5042 Dominant Expression of DCLK1 in Human Pancreatic Cancer Stem Cells Accelerates Tumor Invasion and MetastasisDCLK1

27331

5043 Matrix metalloproteinase-14 mediates formation of bile ducts and hepatic maturation of fetal hepatic progenitor cells.Matrix Metalloproteinase-14

27331

5044 Overexpression of the S100A2 protein as a prognostic marker for patients with stage II and III colorectal cancerstage IIIIIS100A2

27331

5045 Crucial Role of the Aryl Hydrocarbon Receptor (AhR) in Indoxyl Sulfate-Induced Vascular Inflammation

27331

5046 Usefulness of the transfer function index (TFI) for diagnosing peripheral arterial disease in patients with arterial calcification(TFI)

27331

5047 Co-culture with intestinal epithelial organoids allows efficient expansion and motility analysis of intraepithelial lymphocytes

27331

5048 Evaluation of interferon resistance in newly established genotype 1b hepatitis C virus cell culture systemCgenotype 1b

27331

5049 Relationship between regional population and healthcare delivery in Japan

27331

5050 Size of the intracranial optic nerve and optic tract in neonates at term-equivalent age at magnetic resonance imagingMagnetic Resonance Imagingterm-equivalent age

28331

5051 Prognostic value of tropomyosin-related kinases A, B, and C in gastric cancerTrkA, B, C

28331

5052 High-fat diet increases vulnerability to atrial arrhythmia by conduction disturbance via miR-27bmiR-27b

28331

5053 Vessel Wall Inflammation of Takayasu Arteritis Detected by Contrast-Enhanced Magnetic Resonance Imaging: Association withDisease Distribution and ActivityMRI

28331

5054 Semi-in-situ atomic force microscopy imaging of intracellular neurofilaments under physiological conditions through thesandwich methodsemi-in-situ

28331

5055 Expression of connective tissue growth factor in the livers of non-viral hepatocellular carcinoma patients with metabolic riskfactorsconnective tissue growth factor(CTGF)

28331

5056 Transplantation of autologous synovial mesenchymal stem cells promotes meniscus regeneration in aged primates

28331

5057 Michelle Loyola NuylanDown-regulation of LAPTM5 in human cancer cellsLAPTM5

28331

5058 Ipragliflozin improves hepatic steatosis in obese mice and liver dysfunction in type 2 diabetic patients irrespective of bodyweight reduction2

28331

5059 Joint capsule attachment to the coronoid process of the ulna: an anatomic study with implications regarding the type 1fractures of the coronoid process of the ODriscoll classificationODriscoll1

28331

5060 A functional SNP in FLT1 increases risk of coronary artery disease in a Japanese populationFLT1SNP

28331

5061 Monoiodoacetic acid induces arthritis and synovitis in rats in a doseand time-dependent manner: proposed model-specificscoring systems

28331

5062 Loxoprofen sodium induces the production of complement C5a in human serumC5a

28331

5063 Recovery of renal function after radical nephrectomy and risk factors for postoperative severe renal impairment: A Japanesemulticenter longitudinal study

28331

5064 Womens Preference for a Male Acquaintance Enhances Social Reward Processing of Material Goods in the Anterior CingulateCortex

29323

5065 Circadian Clock Regulates Bone Resorption in Mice

28731

5066 BLIZNIUKAnastasiyaAssociation of oral health literacy with oral health behaviour and oral health status in Belarus

28923

5067 Effects of Occlusal Supporting Area on Dynamic Posture against Disturbance by Electrical Stimulation

27331

5068 The facilitatory effects of hyperbaric oxygen treatment on mem-brane bone wound healing in a rat calvarial defect model

27331

5069 Comparison of patient-reported outcomes between immediately and conventionally loaded mandibular two-implantoverdentures: A preliminary study

27331

5070 Osteogenic Potential of Mouse Periosteum-Derived Cell Sorted for CD90 In Vitro and In VivoCD90in vitroin vivo

27331

5071 Short-term intermittent administration of parathyroid hormone facilitates osteogenesis by different mechanisms in cancellousand cortical bone

27331

5072 ROMERO Maria JacintaRosario Hernandez

Casein: A Potential Salivary Phosphoprotein Homologue for Tooth Mineral Regulation Modeling

28331

5073 Impairment of nasal airway under intermittent hypoxia during growth period in rats

28331

5074 Differences between Computer-Based and Paper-Based Assessments of the Clinical Reasoning Competency of DentalStudents

28331

5075 Property of human bone marrow stromal cells derived from bone fragments removed in sagittal split ramus osteotomy

28331

5076 Placenta Mesenchymal Stem Cell Derived Exosomes Confer Plasticity on Fibroblasts

28331

5077 Correlation between body movements and salivary secretion during sedation

28331

5078 Delivery of RANKL-Binding Peptide OP3-4 Promotes BMP-2Induced Maxillary Bone RegenerationRANKLOP3-4BMP-2

28331

5079 Screening tests for predicting the prognosis of oral intake in elderly patients with acute pneumonia

28331

5080 Golgi-Resident GTPase Rab30 Promotes the Biogenesis of Pathogen-Containing AutophagosomesGTPase Rab30

28331

5081 Porphyromonas gingivalis, a Periodontal Pathogen, Enhances Myocardial Vulnerability, thereby Promoting Post-infarct CardiacRupturePorphyromonas gingivalis

28331

5082

Morphological evaluation of the adhesive/enamel interfaces of two-step self-etching adhesives and multimode one-bottle self-etching adhesives.

28331

5083 Dentin bonding performance and interface observation of an MMA-based restorative materialMMA

28331

5084 Novel round cells in urine sediment and their clinical implications

28331

5085 MDCK cells expressing constitutively active Yes-associated protein (YAP) undergo apical extrusion depending on neighboringcell statusYAPMDCK

28331

5086 Chronic Hypersensitivity Pneumonitis With a Usual Interstitial Pneumonia-Like Pattern Correlation Between Histopathologicand Clinical FindingsUIP

28331

5087 Autophagy induced by intracellular infection of Propionibacterium acnesPropionibacterium acnesAutophagy

28331

5088 Subjective insomnia is associated with low sleep efficiency and fatigue in middle-aged women

28331

5089 The hnRNP-Htt axis regulates necrotic cell death induced by transcriptional repression through impaired RNA splicingRNA(hnRNP)-Htt axis

28923

5090 Xanthine oxidoreductase activation is implicated in the onset of metabolic arthritisOA

29323

5091 Kinking of the upper ureter in CT urography: anatomic and clinical significanceCT urography

28923

5092 Popliteal Retrograde Approach is Effective and Safe for Superficial Femoral Artery Chronic Total Occlusion

28923

5093 Effect of Changing the Joint Kinematics of Knees With a Ruptured Anterior Cruciate Ligament on the Molecular BiologicalResponses and Spontaneous Healing in a Rat Model

28923

5094 JAMAL RipaAnti-trypanosome effects of nutritional supplements and vitamin D3: in vitro and in vivo efficacy against Trypanosoma bruceibruceiD3Trypanosoma brucei bruceiin vitroin vivo

28923

5095 Factors associated with positive inhalation provocation test results in subjects suspected of having chronic bird-relatedhypersensitivity pneumonitis

28923

5096 The Indispensable Role of Cyclin-Dependent Kinase 1 in Skeletal DevelopmentCyclin-Dependent Kinase 1

29323

5097 Gene targeting of the transcription factor Mohawk in rats causes heterotopic ossification of Achilles tendon via failedtenogenesisMohawk

28331

5098 Is a Central Venous Catheter Necessary for the Perioperative Management of Esophagectomy? A Prospective Randomized PilotStudy Comparing Two Different Perioperative Regimens

28331

5099 Differential contribution of three immune checkpoint (VISTA, CTLA-4, PD-1) pathways to antitumor responses againstsquamous cell carcinomaVISTACTLA-4PD-1

28331

5100 Effect of enamel margin configuration on color change of resin composite restoration

28331

5101 The role of enamel thickness and refractive index on human tooth colour

28331

5102 Disordered arrangements of basal cells as a prognostic factor for oral epithelial dysplasia: a morphometric study of 96 cases96

28331

5103 Ability of cone-beam computed tomography to detect periapical lesions that were not detected by periapical radiography: Aretrospective assessment according to tooth groupXCT

28331

5104

Effect of strontium ions on calcification of preosteoblasts cultured on porous calcium- and phosphate-containing titanium oxidelayers formed by micro-arc oxidation

28331

5105 Peptide-induced de novo bone formation after tooth extraction prevents alveolar bone loss in a murine tooth extraction model

28331

5106 Moe HtetDecontamination of anodized implant surface with different modalities for peri-implantitis treatment: Lasers and mechanicaldebridement with citric acid

28923

5107 GUAN RuiDentin bonding performance using Weibull statistics and evaluation of acid-base resistant zone formation of recently introducedadhesives

28923

5108 Abhishekhi SHRESTHAEffects of mouthguards on electromyographic activity of masticatory muscles

28923

5109 MAJKUT Patrycja ZaklinaValidation of optical coherence tomography against microcomputed tomography for evaluation of remaining coronal dentinthickness:CT

28923

5110 NGUYEN Thi Kim ChiLAMC2 is a predictive marker for the malignant progression of leukoplakiaLAMC2

28923

5111 ELBASHTI MahmoudEllarousi

Application of Digital Technologies in Maxillofacial Prosthetic Rehabilitation

28923

5112 Bone metabolic microarray analysis of ligature-induced periodontitis in streptozotocin-induced diabetic mice

28923

5113

Unique B7-H1 expression on masticatory mucosae in the oral cavity and trans-coinhibition by B7-H1-expressing keratinocytesregulating CD4+ T-cell-mediated mucosal tissue inflammationB7-H1CD4+ TB7-H1

28923

5114 AsiyaHapaerInvestigating influential factors on the estimation of the origin of a recombinant virus using phylogeographic approach

28923

5115 Dulal Hari PrasadRecombinant expression of a C-type lectin-like receptor Dectin-1 and analysis of its interaction with -glucansCDectin-1-

28923

5116 Systemic Analysis of Atg5-Null Mice Rescued from Neonatal Lethality by Transgenic ATG5 Expression in NeuronsATG5Atg5Atg5

28331

5117 Identification of SATB1 as a Specific Biomarker for Lymph Node Metastasis in Colorectal CancerSATB1

28331

5118 Comparison of Bone Remodeling Between an Anatomic Short Stem and a Straight Stem in 1-Stage Bilateral Total HipArthroplasty

28331

5119 Favorable outcome of intraoperative radiotherapy to the primary site in patients with metastatic prostate cancer

28331

5120 Study on Evaluation of Alanine Aminotransferase(ALT) as Surrogate Marker in Hepatitis Virus Testsurrogate markerALT

28331

5121 Factors Suggestive of Cardiac Complications in Takotsubo Cardiomyopathy:Multicenter Study

29323

5122 Effects and feasibility of exercise therapy combined withbranched-chain amino acid supplementation on musclestrengtheningin frail and pre-frail elderly people requiring long-term care: a crossover trial

29323

5123 Factors associated with 30-day readmission of patients with heart failure from a Japanese administrative database30

29323

5124 Dielectric permittivity change detects the process of blood coagulation: Comparative study of dielectric coagulometry withrotational thromboelastometryROTEM

29323

5125 Expression of hypoxia-inducible factor-1 affects tumor proliferation and antiapoptosis in surgically resected lung cancer1

29323

5126 Human induced pluripotent stem cell-derived hepatic cell lines as a new model for host interaction with hepatitis B virus-

29323

5127 Presentation of Coping Strategies Associated with Physical and Mental Health during Health Check-ups

29323

5128 Differentiation/purification protocol for retinal pigment epithelium from mouse induced pluripotent stem cells as a research tool

29323

5129 Establishment of novel therapy to reduce progression of myopia in rats with experimental myopia by fibroblast transplantation onsclera

28331

5130 Retinol promotes in vitro growth of proximal colon organoids through a retinoic acid-independent mechanism

28331

5131 Impaired striatal dopamine release in homozygous Vps35 D620N knock-in miceVps35 D620N dopamine

28331

5132 Exome Sequencing Identified CCER2 as a Novel Candidate Gene for Moyamoya DiseaseCCER2

28331

5133 Correlations between Cognitive Impairments and Employment Status in Patients with Diffuse Axonal Injury

28331

5134 SUJATA SAKHAExosomal microRNA miR-1246 induces cell motility and invasion through the regulation of DENND2D in oral squamous cellcarcinomamiR-1246DENND2D

28930

5135 Incidence of floating toe and its association with the physique and foot morphology of Japanese children

29323

5136

Scoliosis in osteogenesis imperfecta caused by COL1A1/COL1A2 mutations - genotypephenotype correlations and effect ofbisphosphonate treatmentCOL1A1/COL1A2 mutationphenotype(genotype)

29323

5137 Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as predictors of wound healing failure in head and neckreconstruction

29323

5138

Serial measurement of Wisteria floribunda agglutinin positive Mac-2-binding protein is useful for predicting liver fibrosis and thedevelopment of hepatocellular carcinoma in chronic hepatitis C patients treated with IFN-based and IFN-free therapyIFN-basedIFN-freeCWFA+Mac-2 binding protein

29323

5139 Polymyxin B-immobilized fiber column hemoperfusion mainly helps to constrict peripheral blood vessels in treatment for septicshockB

29323

5140 Effect of N-arachidonoyl-L-serine on human cerebromicrovascular endotheliumN-arachidonoyl-L-serine

28331

5141 Long-term Inflammation Transforms Intestinal Epithelial Cells of Colonic Organoids

28331

5142 Consumer Perception of Inpatient Medical Services

28331

5143 Bone morphogenetic protein-4 modulates proliferation and terminal differentiation of fetal hepatic stem/progenitor cellsBone Morphogenetic Protein-4/

28331

5144 Serum alkaline phosphatase as a predictor of worsening renal function in patients with acute decompensated heart failure

29323

5145 A fiber-optic sorbitol biosensor based on NADH fluorescence detection toward rapid diagnosis of diabetic complicationsNADH

29323

5146 Prognostic significance of PAK4 expression in gastric cancerPAK4

28331

5147 Cortical Actin Alteration at the Matrix-Side Cytoplasm in Lung Adenocarcinoma Cells and Its Significance in Invasion

28331

5148 PGE2 is a direct and robust mediator of anion/fluid secretion by humanintestinal epithelial cells/E2

28331

5149 Treatment of in-stent restenosis with excimer laser coronary angioplasty: benefits over scoring balloon angioplasty aloneScoring balloon

29323

5150 The influence of elective percutaneous coronary intervention on microvascular resistance: a serial assessment using the indexof microcirculatory resistance Index of Microcirculatory Resistance

29323

5151 ST-Segment Elevation on Intracoronary Electrocardiogram After Percutaneous Coronary Intervention is Associated With WorseOutcome in Patients With Non-ST-Segment Elevation Myocardial InfarctionSTST

29323

5152 Inhibitory Effect of Zirconium Coating to Bone Bonding of Titanium Implants in Rat Femur

29323

5153 Inflammatory cytokine levels in synovial fluid 3, 4 days postoperatively and its correlation with early-phase functional recoveryafter anterior cruciate ligament reconstruction: a cohort study

28331

5154 Cadherin 5 expression correlates with poor survival in human gastric cancer5

28331

5155 The ubiquitin hybrid gene UBA52 regulates ubiquitination of ribosome and sustains embryonic developmentUBA52

28331

5156

Use and effectiveness of tocilizumab among patients with rheumatoid arthritis: an observational study from the British Societyfor Rheumatology Biologics Register for rheumatoid arthritistocilizumabBritish Society for Rheumatology Biologics Register for Rheumatoid Arthritis

28331

5157 Direct suppression of autoaggressive CD8+ T cells with CD80/86 blockade in CD8+ T cell-mediated polymyositis models ofmiceCD8+TCD80/86CD8+T

28331

5158 Weekly injections of Hylan G-F 20 delay cartilage degeneration in partial meniscectomized rat kneesHylan G-F20

28331

5159 Hypoxia enhances proliferation through increase of colony formation rate with chondrogenic potential in primary synovialmesenchymal stem cells

28331

5160 Indispensable role of Notch ligand-dependent signaling in the proliferation and stem cell niche maintenance of APC-deficientintestinal tumorNotch

28331

5161

Achieving simplified disease activity index remission in patients with active rheumatoid arthritis is associated with subsequentgood functional and structural outcomes in a real-world clinical setting under a treat-to-targetstrategytreat-to-targetsimplified disease activity index

28331

5162 Factors associated with posttraumatic growth among parents of children with cancer

28331

5163 Sulforaphane promotes murine hair growth by accelerating the degradation of dihydrotestosterone

29323

5164 Basophil tryptase mMCP-11 plays a crucial role in IgE-mediated, delayed-onset allergic inflammation in micemMCP-11IgE

29323

5165 Next-generation sequencing-based small RNA profiling of cerebrospinal fluid exosomesRNA

29323

5166 Learning and Memory Deficits in Male Adult Mice Treated with a Benzodiazepine Sleep-Inducing Drug during the Juvenile Period

29323

5167 Prognostic Impact of Cancer Stem Cell-Like Phenotypes in Pancreatic Ductal Adenocarcinoma

29323

5168 Wnt5a induces renal AQP2 expression by activating calcineurin signalling pathwayWnt5acalcineurin AQP2

29323

5169 Genetic Variants Associated With Susceptibility to Atrial Fibrillation in a Japanese Population

29323

5170

Induction of Peptidylarginine Deiminase 2 and 3 by Dibutyryl cAMP via cAMP-PKA Signaling in Human Astrocytoma U-251MGcellsU-251MGcAMP23cAMP-PKA

29323

5171 Real-time imaging of mast cell degranulation in vitro and in vivoin vitroin vivo

29323

5172 HTLV-1 Tax-Specific CTL EpitopePulsed Dendritic Cell Therapy Reduces Proviral Load in Infected Rats with ImmuneTolerance against TaxHTLV-1 Tax CTLTax

29323

5173 The Basophil-specific Protease mMCP-8 Provokes an Inflammatory Response in the Skin with Microvascular Hyperpermeabilityand Leukocyte InfiltrationmMCP-8

29323

5174 Neuroprotective effects of human umbilical cord-derived mesenchymal stem cells on periventricular leukomalacia-like braininjury in neonatal rats

28331

5175 Clinical Significance of Methylation and Reduced Expression of the Quaking Gene in Colorectal CancerQKI(RNA Binding Protein Quaking)

28331

5176 Physiological and functional changes in the stratum corneum restored by oestrogen in an ovariectomized mice model ofclimacterium

28331

5177 Antimyeloma activity of bromodomain inhibitors on the human myeloma cell line U266 by downregulation of MYCLU266MYCL

28331

5178 SLUG expression is an indicator of tumour recurrence in high-grade endometrial carcinomasSLUG

29323

5179 Perioperative Elevation in Cell-Free DNA Levels in Patients Undergoing Cardiac Surgery: Possible Contribution of NeutrophilExtracellular Traps to Perioperative Renal Dysfunction

29323

5180 Hip, knee, and ankle kinematics during activities of daily living: a cross-sectional study

29323

5181 Increased MFG-E8 expression and its implications in the vascularpathophysiology of cocaine abuseMFG-E8

29323

5182 Prognosis of super-elderly healthy Japanese patients after pacemaker implantation for bradycardia

29323

5183 Novel synthetic compounds with endoperoxide structure damage juvenile stage of Schistosoma mansoni by targeting lysosome-like organelles

29323

5184 Oncogenic roles of the SETDB2 histone methyltransferase in gastric cancerSETDB2

29323

5185 Inhibiting NADPH oxidase protects against long-term memory impairment induced by neonatal sevoflurane exposure in miceNADPH oxidase

29323

5186 Optical Dynamic Analysis of Thrombus Inside a Centrifugal Blood Pump During Extracorporeal Mechanical Circulatory Support ina Porcine Model

29323

5187

Hydrogen sulfide donor NaHS induces death of alveolar epithelial L2 cells that is associated with cellular shrinkage, transgelinexpression and myosin phosphorylationL2NaHS

29323

5188 KAUNGSITHUAssociation of polymorphisms of the transporter associated with antigen processing (TAP2) gene with pulmonary tuberculosis inan elderly Japanese populationTAP2

29323

5189 Is there a differential impact of parity on factors regulating maternal peripheral resistance?

29323

5190 Profiles of serum cytokine levels in Takayasu arteritis patients: Potential utility as biomarkers for monitoring disease activity

29323

5191 The Efficacy of Isochronal 3D Mapping-Based Ablation of Ventricular Arrhythmia Running head: isochronal mapping, ablation3

29323

5192 Improvement in the Quality of Life and Exercise Performance in Relation to the Plasma B-Type Natriuretic Peptide Level AfterCatheter Ablation in Patients With Asymptomatic Persistent Atrial FibrillationBNPQoL

29323

5193

Critical Contribution of Tyr15 in the HIV-1 Integrase (IN) in Facilitating IN Assembly and Nonenzymatic Function through the INPrecursor Form with Reverse TranscriptaseHIV-115

29323

5194 Impaired degradation of WNK by Akt and PKA phosphorylation of KLHL3PKAAktKLHL3WNK4

29323

5195 Trogocytosis of peptideMHC class II complexes from dendritic cells confers antigen-presenting ability on basophilsMHCII

29323

5196 Khin Thet Thet ZawAssociation of ZFHX3 gene variation with atrial fibrillation, cerebral infarction, and lung thromboembolism: An autopsy studyZFHX3

29323

5197 Indwelling Voice Prosthesis Insertion After Total Pharyngolaryngectomy With Free Jejunal Reconstruction

29323

5198

Severe damage to the placental fetal capillary network causes mid- to late fetal lethality and reduction in placental size inPeg11/Rtl1 KO micePeg11/Rtl1 KO

29323

5199 Life-Threatening Ventricular Arrhythmia and Brugada-Type ST-Segment Elevation Associated With Acute Ischemia of the RightVentricular Outflow TractBrugadaST

29323

5200 Enhancement of 5-aminolevulinic acid-based fluorescence detection of side population-defined glioma stem cells by ironchelation5-side population

29323

5201

Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemicrheumatic diseases: results from a non-blinded, randomized controlled trial

29323

5202 Human eosinophils constitutively express a unique serine protease, PRSS33PRSS33

29323

5203 Fibrous Synovium Releases Higher Numbers of Mesenchymal Stem Cells Than Adipose Synovium in a Suspended SynoviumCulture Model

29323

5204 ARADHAN SARKARDomain analysis of Ras-association domain family member 6 upon interaction with MDM2RASSF6MDM2

29323

5205 Complementary Critical Functions of Zfy1 and Zfy2 in Mouse Spermatogenesis and ReproductionZfy1 Zfy2

29323

5206 LAPTM4B-35 is a novel prognostic factor for glioblastomaLAPTM4B-35

29323

5207 Computational fluid dynamic study of nasal respiratory function before and after bimaxillary orthognathic surgery with bonetrimming at the inferior edge of the pyriform aperture

28331

5208 Assessment of cervical demineralization induced by Streptococcus mutans using swept-source optical coherence tomographyStreptococcus mutans

28331

5209 Characterizing Genetic Transitions of Copy Number Alterations and Allelic Imbalances in Oral Tongue Carcinoma Metastasis

28331

5210 NGUYEN VO Ngoc TrangLigature induced peri-implantitis: tissue destruction and inflammatory progression in a murine model

29323

5211 Effect of thermal cyclic stress on acid resistance of resin-infiltrated incipient enamel lesions in vitro

29323

5212 Monitoring of cariogenic demineralization at the enamel-composite interface using swept-source optical coherence tomographySS-OCT

28331

5213 Development and modification of a device for three-dimensional measurement of orthodontic force system: The V-bend systemre-visitedV

28331

5214 The influence of elastic moduli of core materials on shear stress distributions at the adhesive interface in resin built-up teeth.

28331

5215 Diffusion tensor imaging of the inferior alveolar nerve using 3T MRI: a study for quantitative evaluation and fibre tracking MRI

29323

5216 Factors associated with mucosal pain in patients with partial removable dental prostheses

28331

5217 Effects of increased occlusal vertical dimension on the jaw-opening reflex in adult rats

28331

5218 Optical analysis of enamel and dentin caries in relation to mineral density using swept-source optical coherence tomography

28331

5219 Influence of implant number on the movement of mandibular implant overdentures

28331

5220 Peptide drugs accelerate BMP-2-induced calvarial bone regeneration and stimulate osteoblast differentiation through mTORC1signalingBMP-2 mTORC1

28331

5221 ZBTB16 as a Downstream Target Gene of Osterix Regulates Osteoblastogenesis of Human Multipotent Mesenchymal StromalCellsOsterixZBTB16

28331

5222 28331

5223 Effects of citalopram on jaw-closing muscle activity during sleep and wakefulness in mice

28331

5224 Effect of brushing timing after erosive challenge on enamel loss in situ: white light interferometer and nanoindentation studyinsitu

29323

5225 A finite element analysis of stress distribution in roots with different types of post systems

28331

5226 Effects of teeth clenching on the soleus H reflex during lower limb muscle fatigueH

28331

5227 Application of addition-cured silicone denture relining materials to adjust mouthguards

28331

5228 Double-layered cell transfer technology for bone regeneration2

28331

5229 High-frequency pulsed low-level diode laser therapy accelerates wound healing of tooth extraction socket: an in vivo study

28331

5230 Morphological evaluation of artificial caries-affected dentin after applying FCP-COMPLEXFCP-COMPLEX

28331

5231 Drug delivery and transmission of lidocaine using iontophoresis in combination with direct and alternating currents-

29323

5232 AKTAR Most DilrubaValue of real-time tissue elastography for squamous cell carcinoma of the tongue

28331

5233 Value of real-time tissue elastography for squamous cell carcinoma of the tongue

28331

5234 Dentin Bonding Durability of Two-step Self-etch Adhesives with Improvement of Degree of Conversion of Adhesive Resins

28331

5235 Involvement of CX3CL1 in the Migration of Osteoclast Precursors Across Osteoblast Layer Stimulated by Interleukin-1IL-1CX3CL1

28331

5236 The transcription factor mohawk homeobox regulates homeostasis of the periodontal ligamentmohawk homeobox

28331

5237 KULKARNI TejaswiniVaman

DNA-based culture-independent analysis detects the presence of Group A Streptococcus in throat samples from healthy adultsin JapanDNAA

28930

5238 Distinct interacting core taxa in co-occurrence networks enable discrimination of polymicrobial oral diseases with similarsymptoms

29323

5239 Effect of Chewing on Body Sway in Patients Wearing Dento-Maxillary Prosthesis after Head and Neck Tumor Resection

29323

5240 Profilin Expression is Regulated by Bone Morphogenetic Protein (BMP) in Osteoblastic Cells.Profilin(BMP)

29323

5241 The influence of the framework thickness on the surface strain of the 3-unit Zirconia Resin-bonded fixed dental prosthesesunder the functional loading

29323

5242 Receptor tyrosine kinase amplification is predictive of distant metastasis in patients with oral squamous cell carcinoma

29323

5243

PDMP, a ceramide analogue, acts as an inhibitor of mTORC1 by inducing its translocation from lysosome to endoplasmicreticulumPDMPmTORC1mTORC1

29323

5244 The ball-on-disk cyclic wear of CAD/CAM machinable dental composite and ceramic materialsCAD/CAM

28331

5245 The Morphological Evaluation of Denture Space in Glossectomy Patients

28331

5246 Tumurkhuu TsasanAssociation between maternal education and malocclusion in Mongolian adolescents: a cross-sectional study

28331

5247 New approach to transfect NF-kappaB decoy oligodeoxynucleotides into the periodontal tissue using ultrasound-microbubblemethodNF-B

28331

5248 28331

5249 Association between chewing-stimulated salivary flow under the effects of atropine and mixing ability assessed using a color-changeable chewing gum

28331

5250

Effect of jaw-opening exercise on prevention of temporomandibular disorders pain associated with oral appliance therapy inobstructive sleep apnea patients: A randomized, double-blind, placebo-controlled trialOA

28331

5251 Hydrophilic nano-silica coating agents with platinum and diamond nanoparticles for denture base materials

28331

5252 Evaluation of corrosion resistance of implant-use Ti-Zr binary alloys with a range of compositionsTi-Zr

28331

5253 An objective estimation of the removability of three home reliners

28331

5254 An in situ hybridization study of Hyaluronan synthase (Has) mRNA in developing mouse molar and incisor tooth germsin situ hybridization(Has) mRNA

29323

5255 White spot lesion remineralization by sugar-free chewing gum containing bio-available calcium and fluoride: A double-blindrandomized controlled trialwhite spot

29323

5256

An in situ hybridization study of perlecan, DMP1, and MEPE in developing condylar cartilage of the fetal mouse mandible andlimb bud cartilage.perlecanDMP1MEPE mRNAin situ hybridization

29323

5257 Synthesis and enhanced bone regeneration of carbonate substituted octacalcium phosphate

29323

5258

Effect of unilateral nasal obstruction on the craniofacial muscles in growing rats

29323

5259 Stress distribution in luting agents with different post and core systems

29323

5260 Non-invasive optical assessment of biofilm-induced demineralization on human teeth with and without resin-based materialapplication

29323

5261

Beta Adrenergic Receptor Stimulation Suppresses Cell Migration in Association with Cell Cycle Transition in Osteoblasts - LiveImaging Analyses Based on FUCCI System-FUCCI

29323

5262

Effect of antimicrobial photodynamic therapy using rose bengal and blue light-emitting diode on Porphyromonas gingivalis invitro: Influence of oxygen during treatmentin vitroLEDPorphyromonas gingivalis

29323

5263 Histone methyltransferase Setdb1 is indispensable for Meckel's cartilage developmentSetdb1

29323

5264 RAKPRASITJutaratHealthcare use for communicable diseases among migrant workers in comparison with Thai workers

28930

5265 Wound healing efficacy of a 660-nm diode laser in a rat incisional wound model660-nm

28331

5266 AL-SOBAIHISaberAbdullahHizam

Undernutrition among children under 5 years of age in Yemen: Role of adequate childcare provided by adults under conditions offood insecurity

28930

5267 Deletion of conserved sequences in IG-DMR at Dlk1-Gtl2 locus suggests their involvement in expression of paternallyexpressed genes in miceDlk1-Gtl2 IG-DMR

29323

5268 28331

5269 Development and evaluation of community residents participating in livelihood support system for community-dwelling cancerpatients (CPL-CCP system)

28331

5270 What prevents critically ill patients with respiratory failure from using noninvasive positive pressure ventilation: A mixed-methods study(NPPV)

28331

5271 28331

5272 Use of Traditional Birth Practices by Chinese Women in the United States

29323

5273 Pancreatic cysts in general population on ultrasonography: Prevalence and development of risk score

29323

5274 Effects of serum amyloid A on the structure and antioxidant ability of high-density lipoproteinSAAHDL

29323

5275 Paraoxonase 1 associated with high-density lipoprotein transfers to oxidized low-density lipoprotein depending on the degree ofoxidation Paraoxonase1

29323

5276 Application of low-vacuum scanning electron microscopy in cytopathology: To what extent can adenocarcinoma bemorphologically distinguished from squamous cell carcinoma in lung cancer?

29323

5277 Cholesterol Efflux Capacity of Apolipoprotein A-I Varies with the Extent of Differentiation and Foam Cell Formation of THP-1CellsTHP-1apoA-I

29323

5278 Studies on the effects of the long-term administration of melatonin on blood metabolites in aging mice

28331

5279 Investigation of pathway biomarkers of hepatocellular carcinoma based on gene regulatory networks

28331

5280

Analysis of the function of stress-activated protein kinase MKK7 in adult nervous systemMKK7

29323

5281 Elucidation of the molecular mechanisms underlying active YAP-induced apical extrusion in mammalian cellsYAP

29323

5282 Development of C3-Exomethylene Sialic Acid Derivatives Toward Functional Analysis of Sialidase3

29323

5283 DILIHUMAER AiniwaerDevelopment of novel modulators for transcriptional co-activator TAZ involved Hippo pathwayHippoTAZ

29323

5284 MEDZHIDOV NazimEndosomal trafficking and persistence of the antigen-B cell receptor complex and their significance in B cell activationBB

29323

5285 Fluorination with Anionic Phase-Transfer Catalysts

29323

5286 Synthetic Studies on Chloroalkene Dipeptide Isosteres as Peptidomimetics

29323

5287 Development of Chemical Probes Based on an 8-Azacoumarin Chromophore8-Azacoumarin

29323

5288 29323

- 1 -

Dominant Expression of DCLK1 in Human Pancreatic Cancer Stem Cells Accelerates Tumor Invasion and Metastasis

DCLK1 DCLK1 DCLK1 DCLK1 DCLK1 85

5 6%1990

- 2 -

ODCZsGreen2 KLM1BxPC3Gdeg-KLM1Gdeg-BxPC3

Gdeghigh-KLM1Gdeghigh-BxPC3 in vitro sphere in vivo Gdeghigh

2 ODC Gdeg-KLM1Gdeg-BxPC3 1In vitro Gdeghigh Gdeglow sphere Double Chamber Assay In vivo GdeghighGdeglow Gdeghigh

Gdeghigh Gdeghigh GdeglowRNA GdeghighFC>2 483 (FC

- 3 -

DCLK1 DCX 70 N

ST C 2 DCX X double cortex syndromeDCX DCLK1 DCLK1 DCLK1

DCLK1 DCLK1 let-7 mir200 EMT EMT Gdeghigh Gdeglow RNA RNA data not shownCD133+/CXCR4+CD133+/CXCR4- DCLK-1 RNA Gdeghigh

CXCR4 EMT DCLK1 Gdeghigh ROCK DCX DCLK-1 DCLK1

DCLK1 DCLK1

DCLK1

( 1 )

5042

DCLK1 DCLK1

85

% DCLK1

in vitro, in vivo

DCLK1 DCLK1

( 2 )

DCLK1 DCLK1 .

- 1 -

Matrix metalloproteinase-14 mediates formation of bile ducts and hepatic maturation of fetal hepatic progenitor cells.

()

Matrix Metalloproteinase-14 (MMP-14) MMP I MMP TGF-MMP-14 in vitro MMP-14 in vivo MMP-14

MMP-14 EGFR-MAPK MMP-14

CD13EpCAMNCAMDlk oncostatin M Notch-Hes1 TGF-Wnt--catenin

MMP-14 20 MMP MMP (MT1-MMP) I MMP MMP-2TGF- TGF-MMP family MMP-14

- 2 -

VEGF

G-CSF MMP-14 MMP-14

MMP-14 RT-PCRin vitro 14.5 E14.5OSMEHS gel I EHS gel Cyst MMP-14 MMP-2 MMP-14 In vivo MMP-14 PCR MMP-14 MMP-14 VEGF MMP-14 Western blot

MMP-14

mRNA 60

in vitro MMP-14

CystMMP-14CystHNF1NotchHesJagged1C-mycMMP-2 MMP-2 MMP-14 MMP-14

MMP-14 Cyst

in vivo 1 (P1) MMP-14 MMP-14 E14.5

- 3 -

P1 E14.5 MMP-14 EGFR MMP-14 P1 MMP-14 MMP-14 PCR E16.5 ductal plateP1 MMP-14 HGF Met

EGFR RT-PCR P1 EGFR MMP-14 MAPK family(p38 MAPKERKJNK)MMP-14 VEGF VEGF MMP-14 MMP-14 EGFR-MAPK

MMP-14

MMP-14 MMP-14

in vitro in vivo MMP-14

MMP-14 in vivo EGFR-MAPK MMP-14 MMP-14 EGFR transactivation MMP-14 MMP-14 EGFR transactivation EGFR MAPK in vivo MMP14 P1 in vitro

Cyst ductal plate in vitro MMP-14

MMP-14 in vitro MMP-14 Cyst in vivoin vitro MMP-14

- 4 -

in vitro VEGF MMP-14 VEGF MMP14 VEGF MMP-14 MMP-14 MMP-14

MMP-14 MMP-14 oval cell MMP-14 oval cell MMP-14 MMP-14

( 1 )

5043

MMP-14 MMP-14

MMP-14

MMP-14

in vitro MMP-14

in vivo RT-PCRWestern blot MMP-14

MMP-14 in vitro in vivo MMP-14

MMP-14

( 2 )

.

- 1 -

Overexpression of the S100A2 protein as a prognostic marker for patients with stage II and III colorectal cancer

stage IIIII 125 stage IIIII

161 S100 calcium binding protein A2S100A2S100A2 S100A2 S100A2 stage IIIII 20

stage II 15stage III 30TNM personalized medicine SNP

SNP array microarray S100A2 stage IIIII

2002 2009 stage IIIII 125 n = 32n = 93GeneChipHuman Mapping 250K Sty Array ; Affymetrix GeneChip Human Genome U133 Plus2.0 Array ; Affymetrix 161 ImmunohistochemistryIHC

- 2 -

9 S100A2PROX1TCN1PROM1

CHRM3ZNF678CREB5PPARGC1AATF6 S100A2 S100 family S100 family S100A2 stage IIIII

RT-PCR S100A2 mRNA P < 0.05 S100A2 IHC

S100A2 n = 91n = 70 S100A2

S100A2 stage IIIII S100A2

S100A2 S100A2 S100A2 StageIIIII S100A2 S100 family S100 family

S100 family

S100A2 EF S100A2 TGF-p53 cell cycle S100A2 S100A2 TGF-

stage IIIII S100A2S100A2 S100A2

stage II

- 3 -

stage II T4 12

stage III TNM 7 IIIAIIIBIIIC stage IIIA stage III stage II S100A2 stage IIIII stage IIIII

S100A2 S100A2 target

( 1 )

5044

stage IIIII

125 stage IIIII

161 S100 calcium binding protein A2S100A2S100A2 S100A2 S100A2 stage IIIII stage IIIII

stage IIIII

S100A2 mRNA S100A2 stage IIIII 100A2 S100A2 n = 91n = 70 S100A2 S100A2 stage IIIII S100A2

( 2 )

stage IIIII S100A2 S100A2 S100A2 stage IIIII .

- 1 -

Crucial Role of the Aryl Hydrocarbon Receptor (AhR) in Indoxyl Sulfate-Induced Vascular Inflammation

Indoxyl SulfateISCKD

Aryl hydrocarbon ReceptorAhRIS IS-AhR AhR eAhR KOIS TNF- IS eAhR KO IS human umbilical vein endothelial cells: HUVEC AhR siRNAsiAhRISTNF-IS AhR E-selectin AhR IS c-jun N-terminal domain kinaseJNKNF-B Luciferase assay E-selectin IS AhR AP-1 E-selectin IS AhR CKD

CKD

CKD

E-selectin

- 2 -

IS

CKD 50 IS

IS IS JNK NF-B E-selectin

IS IS

2010 Schroeder AhR IS AhR basic helix-loop-helix Per-Arnt-Sim regulatory protein superfamily 2378-tetrachlorodibenzo-p-dioxinTCDD AhR xenobiotic response elementXREcytochrome p450 (Cyp) 1A1 Cyp1b1 TCDD apoE IS AhR in vivo in vitro

AhR-loxPAhRfx/fx Tie2-cre eAhR KO AhRfx/fx eAhR KO IS 079 mmol/L 2 100 g/kg TNF-3 HUVEC siAhR non-targeting siRNAsiCont

02 20 mmol/L IS 20 TNF- HL-60 non static rotational assay mRNA PCR E-selectin promoter -166 ~ +107 pGL3-basic luciferase vectorNF-ELAM-1 vector NF-ELAM-1 mNF-ELAM-1 vectorNF-ELAM-1 AP-1 NF-ELAM-AP-1 vectorCRE NF-ELAM-CRE vector Luciferase assay

- 3 -

AhRfl/fleAhR KO IS IS

AhRfl/fl IS eAhR KO IS

HUVEC IS AhR XRE Cyp1a1 Cyp1b1 mRNA siAhR IS E-selectin siAhR IS c-jun N-terminal domain kinaseJNKNF-B NF-ELAM-1 vector Luciferase assay IS mNF-ELAM-1 vector IS NF-ELAM-AP-1 vector IS NF-ELAM-CRE vector IS IS AP-1 siAhR IS CRE IS AhR JNK

NF-B E-selectin AhR agonist HUVEC AhR agonist ROS AhR antagonist IS AhR IS AhR IS NADPH oxidase apocynin NF-B AhR NF-B

AP-1 E-selectin NF-ELAM-1 AP-1 ATF-2 CRE CREBIS E-selectin AP-1 AP-1 AhR IS AhR AP-1 AhR AP-1 AhR AP-1 AP-1 ATFaATF-2ATF-3c-junjunB junD siAhR ATF-2 c-jun AhR AhR AP-1

eAhR KO IS AhR CKD IS CKD IS

- 4 -

apoE AhR agonist P-selectin

IS 015~02 mmol/L CKD CKD IS AhR

IS AhR AP-1 E-selectin CKD IS-AhR

( 1 )

5045

IS IS AhR

AhR TNF

AhR siRNAsiAhR

IS AhR E-selectin

Luciferase assay IS AhR AP-1 E-selectin

IS

AhR in vivo

IS

( 2 )

- 1 -

Usefulness of the transfer function index (TFI) for diagnosing peripheral arterial disease in patients with arterial calcification

Abstract Objective: The prevalence of patients with peripheral arterial disease (PAD) is increasing, and these subjects also often have diabetes mellitus (DM) and/or chronic renal failure treated with hemodialysis (HD). Measurements of the ankle brachial pressure index (ABI) are widely used to screen for peripheral artery disease (PAD). Because medical calcification frequently develops in patients with DM or HD, ankle brachial pressure index (ABI) may provide false-negative result in some patients with arterial calcification, resulting in a misdiagnosis of PAD. Therefore, It is very important to estimate the presence of PAD associated with calcification using noninvasive methods to reduce the risk, time and costs associated with invasive modalities, such as angiography. The aim of this study was to investigate which parameters among the ABI, toe brachial pressure index (TBI) and transfer function index (TFI) may be used to diagnose more accurately patients with/without arterial calcification in the ankle who undergo any type of diagnostic imaging examination. Patients and Methods: A total of 67 patients with PAD, with a mean age of 72.5 8.1 years, were enrolled in this study. The ABI and TBI were measured using peripheral vascular diagnostic equipment (VasoGuardTM), The TFI was measured at the ankle (TFIankle) and at the calf (TFIcalf) using pulse volume recording. The area under the curve (AUC) was calculated according to the receiver operating characteristic curve, and the cutoff value was determined. Results: There was a strong correlation between the ABI and TBI in the no calcification in the distal crural arteries (r = 0.75). However, no correlations were observed in the railroad track-type calcification (r = 0.11). When an ABI of 0.90 was defined as the criterion for diagnosing PAD, the sensitivity and specificity were 69.8%, and 100%, respectively, although the AUC was 87%. When the cutoff value for TFIankle was set at 1.025, the sensitivity was 83.7%, the specificity was 92.3%, whereas the AUC was 90%. The sensitivity and specificity of TFIcalf (cutoff value: 1.025) was 79.1% and 92.3%, respectively, whereas AUC was 89%.

- 2 -

Discussion Arterial calcification is associated with obesity, hypertension, dyslipidemia, and diabetes. Diabetes and calcification were found to have a close relationship in the present study, however, patients with DM exhibited in all three groups. Because diabetic patients with medial calcification have a significantly higher incidence of lower extremity amputations, the early detection of calcification may provided information predicting critical limb ischemia in diabetic patients. Intimal and medial calcification cannot be differentiated using non-contrast MDCT images. Plain x-ray findings and/or the pathological diagnosis can be used to identify the classification of calcification and plain X-rays can be employed to assess the degree and type of calcification, which may be helpful to progression of calcification and arterial disease in diabetic patients. PAD is highly prevalent in HD patients, although it is frequently underdiagnosed. In patients with HD, a high age, diabetes, hypercalcemia and hyperphosphatemia have been described to be associated with a higher risk of amputation, which may contribute to arterial calcification for the onset of PAD in this population. In the current study, there were statistically significant differences in the incidence of arterial calcification based on the use of HD. In particular, railroad tracktype calcification was detected in 25%, 67% and 100% of the patients in the DM, HD, and DM with HD groups, respectively. The results also showed that all patients with HD had railroad tracktype calcification in the ankle. The reliability of ABI measurements is considered to be very low in HD patients. The early detection of PAD is also highly important in order to prevent major amputation; therefore, plain X-rays should be obtained especially in HD patients. The ABI is a useful objective parameter to document the presence of lower-extremity PAD. Usually, an ABI of less than 0.90 has been shown to have a sensitivity of 90% and specificity of 98% to detect significant arterial stenosis (luminal stenosis 75%). A high ABI value ( 1.30) reflects non-compressible arteries at the ankle, which may be related to distal arterial calcification. The TBI can be used and valuable to evaluate the presence or severity of PAD in the lower extremities because digital arteries are much less susceptible to medial calcification. Digital arterial pressures are normally lower than brachial pressures. In the present study, the correlations between the ABI and TBI in three different groups were evaluated which showed a significant strong correlation only in the no calcification group (r = 0.75), whereas no correlation was observed in the railroad tracktype calcification group (r = 0.11). Because there was a significant strong correlation in the no calcification group, the TBI may be used to evaluate the actual lower limb blood flow. In addition, there was a weak correlation in the plaque-type calcification group, which possibly indicated that any type of calcification might result in false-negative ABI values. Therefore, the TBI should be measured in patients with neither DM nor HD, as one-third of the patients in this group had plaque-type calcification.

- 3 -

It is very important to estimate the presence of PAD associated with calcification using noninvasive methods to reduce the risk, time and costs associated with invasive modality. Therefore, we attempted to elucidate whether resting parameters are more useful for assessing the PAD in patients with calcification. Consequently, the sensitivity of an ABI 0.9, the standard cutoff value for diagnosing PAD, was only 68.9% in the present study, while the AUC remained relatively low (87%). Meanwhile, a cutoff value for TFIankle of 1.025 for detecting PAD showed sufficient sensitivity, specificity and AUC values, at 83.7%, 92.3%, and 90%, respectively. The AUC for the ABI may be poor because the ABI values often provide false-negative results for diagnosing PAD due to the presence of arterial calcification. Hence, the ABI is not useful for appraising the ischemic status in patients with arterial calcification.

The TFI is a more sensitive and specific tool for detecting PAD, despite the fact that railroad-track type arterial calcification is observed in 90% of all patients with DM and/or HD. The TFI is also an efficient parameter for executing infrainguinal vein graft surveillance because vein grafts remain compliant, similar to native arteries. Whereas Nakashima have reported that TFIcalf was more useful parameter than the ABI and TFIankle to diagnose claudicants (recovery ability index > 0.6) even in diabetic patients. The similar results were obtained that TFIankle was the best parameter to diagnose PAD even in patients with DM and/or HD. In contrast, the TFI decreased in the patients with prosthetic graft and/or stent placement at the proximal arteries, including the aortoiliac and femoropopliteal regions. Therefore, PAD patients, who have undergone bypass surgery using prosthetic grafts or stent placement were excluded from this study. PVR was first introduced to be an accurate modality for documenting lower extremity PAD in the 1970s. Plethysmography is also an excellent modality for diagnosing PAD, even in patients with DM and/or HD; however, it was not used widely in the clinical settings. The pulsatile pressure and blood flow must be calculated to determine the impedance in the arterial segment, which is associated with theoretical and practical problems. In the current study, the multi-cuff unit recorded pulse volume waveforms at 10 sites simultaneously, which were subsequently analyzed using Fourier and Laplace transformation to produce the TFI automatically, without examiner dependency or technical demands. This is why the TFIs were more resistant to the effects of arterial calcification than the ABI. The PVR can evaluate the ischemic severity even in patients with arterial calcification, which can not be compressed by a cuff. TFI measurement using PVR is a promising method for appraising arterial disease due to its noninvasiveness as well as several features of being simple, painless and operator independent. Simple assessments of PAD using the TFI in patients with arterial calcification may play an important role in more accurately assessing the prevalence of PAD particularly in subjects with DM and HD.

- 4 -

Conclusions: A cutoff value of TFIankle 1.025 exhibits higher sensitivity for detecting the presence of PAD than the ABI and TFIcalf. Therefore, the TFIankle is useful for estimating the presence of PAD in patients with arterial calcification.

PAD/() DM HD (ABI)(PAD)-(ABI), (TBI), (TFI) PAD 67 134 72.58.1 (VasoGuardTM) ABI, TBI TFI TFIankle(TFIcalf)AUC ROC ABI TBI (r = 0.75)(r = 0.11)ROC PAD ABI:0.9 69.8%100%AUC87%TFI 1.025 TFIankle 83.7%, 92.3%AUC90 %TFIcalf 79.1%,92.3%,AUC89% TFIankle1.025 ABI TFIcalf PAD , TFIankle PAD

( 1 )

5046

transfer function index (TFI)

PAD, PAD ankle brachial pressure index (ABI)

102 192 2 ABI, toe brachial pressure index (TBI), TFI ROC 3 TFI

TFI PAD TFI

- 1 -

Co-culture with intestinal epithelial organoids allows efficient expansion and motility analysis of intraepithelial lymphocytes

Intraepithelial Lymphocyte; IELIEL IEL in vitro Intestinal Epithelial Cell; IEC IEC IEL IEL TCRTCR 2 4 IEL T IELs T IELs MEK1/MEK2 2 T IELT IEL IEL IEC IEL in vitro

- IELIEL 510 1 IEL TCR Type aIEL TCR Type b

- 2 -

IEL IEL in vitro IEL IEL IEL IEC IEC

IEL

IEL IEL IEC IEC IEL IEL IEC IEC 2 IEL IEL IEL 3 IEL IEL EGFP EGFP-tg EGFP H2B-EGFP IELEGFP IEL Hoechst33342

Imaris IEL IEL Day10.21 0.06 CD3 IEL Day3 IEL IEL IEC IEL IEC 2 IEL 3 IEL 6.9 0.8 100 GFP CD3 IEL IEC Day7 IEL

- 3 -

IEL IL-2,IL-7,IL-15 Day7 2 1 2 4 IEL IEL T IEL T IEL IEL IEL IEL IEL IEL IEC IEL EGFP-tg IEL IEL

IEC IEL IEL H2B-EGFP-tg IEL WT IEC IEL 5.07 0.27 9.67 0.60 m/min in vivo T IEL 3.8 0.17.7 m/min in vitro IEL in vivo in vitro IEL T IEL T IEL MEK1/MEK2 PD184532 T IEL 20T IEL T IEL T IEL IEL T IELT IEL in vitro IEL T IEL T IEL IEL

( 1 )

5047

IEL TCR TCR in vitro

IEL IEL IL-2, IL-7, IL-15

IEL IEL 5.070.27,

9.670.60m/min 2 in vivo IEC

IEL H2B-EGFP IEL IEL

IEC IEL IEC

( 2 )

.

- 1 -

Evaluation of interferon resistance in newly established genotype 1b hepatitis C virus cell culture system

C HCVgenotype 1b (GT1b)(IFN; interferon) 70/91 IFN HCV GT1b HCV cell culture system: HCV ccTPF1-M170T 70/91

TPF1-M170T 70/91 HCV GT2a JFH1 IFN 70/91 GT1b JFH1 IFN HCV GT1 Peg-IFN+ 72 sustained virological response

(SVR) 50%direct-acting antiviral agentsDAAs2014 IFN2SVR80-90% DAAs DAAs SVR IFN DAAs

in vitro GT1b HCV cc

HCV GT2a HCV ccJFH1 70/91 GT1b HCV ccTPF1-M170T 70/91 IFN

- 2 -

GT1b HCV ccTPF1-M170T 70/91 IFN

R70QL91MR70QL91M Core WT Huh7-ALS32.50 3

CLIA NS5A

IFN TPF1-M170T 70/91 HCV GT2a JFH1 4 IFN-alpha 2a 48effective concentration 50% (EC50) IFN TPF1-M170T 70/91

50-60% JFH1 70%JFH1

TPF1-GDDNS5B GDD 70/91 day1-5 TPF1-GDD TPF1-M170T 70/91 L91M NS5A TPF1-M170T 70/91HCV GT2a JFH1IFNJFH1 IFN-alpha-2b EC50 1.411.29 IU/ml Core WT, R70Q, R70QL91M 5.10 1.27 IU/ml, 3.23 0.37 IU/ml, and 3.81 1.05 IU/ml. L91M L91M EC50 17.1 6.86 IU/ml GT1b Core WT JFH1 GT1b IFN GT1b IFN HCV cc 70/91 HCV GT1b IFN

HCV cc RT-PCR HCV-RNA TPF1-GDD RNA

HCV cc JFH1 RT-PCR HCV-RNA 10

- 3 -

RNA RNA RNA HCVTPF1-GDD HCV HCV NS5A RNA GT1bHCV cc IFN IFN GT 1b 2a HCV cc IFN

Funaoka R70Q L91M Tasaka-Fujita R70Q L91M GT 2a GT 1b/1a NS GT 2a NS replication complex GT 1b 70/91 IFN Funaoka JFH1 HCV cc Tasaka-Fujita 70/911b/1a 70/91 IFN HCV MHC Class I IFN IFN HCV JAK/STAT MHC class I cytotoxic T cell IFN

Huh7-AL32.50 IL28B SNPs IFN 70/91 IFN IFN IL28B IFN IFN

IFN IL28B SNPs IFN HCV GT 1b GT 2a IFN

IFN HCV

( 1 )

5048

C (HCV) Ib (IFN) HCV genotype 1b

genotype IFN

HCV

genotype 1b IFN genotype IFN IFN

C genotype 1b RNA plasmid pTPF1-M170T

RNA Huh-7-ALS32.50 IFN RNA

HCV genotype IIa Ib IFN IFN Ib IFN HCV Ib genotype Ib

( 2 )

.

- 1 -

Relationship between regional population and healthcare delivery in Japan

. 1985

3 901 2

481% 420

. 1950

1980 1985 1990

2014

- 2 -

2010 2011 2010

2010 349 IBM SPSS Statistics23 2000 2010 2010 2011 2010

.

2010 2190 036 539 2011 10610 038 265

r=0772, p

- 3 -

10 2

. 1985

3 90%

1

14

- 4 -

10 100

( 1 )

5049

2000 2011

1 1 2

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.

- 1 -

Size of the intracranial optic nerve and optic tract in neonates at term-equivalent age at magnetic resonance imaging

Term-equivalent age (postmenstrual age 37 0 41 6 )term-equivalent age reference value 62 term-equivalent age MRI

2.70.2 mm1.70.2 mm3.50.5 mm2 1.50.1mm1.60.1mm2.00.2mm2 postmenstrual age 95%0.07(postmenstrual age in weeks) 0.46 mm0.17(postmenstrual age in weeks) 4.0 mm2

15-80%

gold-standard MRI

MRI

MRI term-equivalent age term-equivalent age 1

- 2 -

reference value

2013 1 2014 9 1.5-Tesla MRI 174

0 1) term-equivalent age2) MRI 3) 4) 4 study 174 90 term-equivalent age 66 62 62 59 1 38 Table 1 MRI

T2-weighted turbo spin echo image(TR: 5,400 ms, TE: 91 ms, NEX: 1, Echo Train Length: 1729, slice thickness: 4 mm, intersection cap: 0 mm, Field of View: 210 mm, matrix: 256256)axial sagittal 2 Fig. 1 R Table 2 postmenstrual

ageTable 3 postmenstrual age Fig.2 Fig.3 Linear regression model term-equivalent age

postmenstrual age

- 3 -

gold-standard CTMRI CT MRI

MRI quantitativeBirkebaek1

- 4 -

three-dimensional steady-state free precession

term-equivalent age

Postmenstrual age

( 1 )

5050

MRI

gold-standard MRI

term-equivalent age

1. 62 term-equivalent age MRI 2.70.2 mm1.70.2 mm3.50.5 mm2 1.50.1mm1.60.1mm2.00.2mm2

2. postmenstrual age

term-equivalent age

MRI

2013 2014 MRI 0

MRI

( 2 )

MRI

postmenstrual age 2 2

.

- 1 -

Prognostic value of tropomyosin-related kinases A, B, and C in gastric cancer

Trk TrkA, B, C 2003-2007 221 TrkA, B, C TrkA, B, C (p=0.022, p

- 2 -

Trk TrkA, B, C 3 Trk Trk Ras Trk p75NT TrkA, B, C

TrkA, B, C

2003 3 2007 12 221 3-6 61

4 0123 4 025%126-50%251-75%375% 10% 4 4 RNA cDNA

RT-PCR Trk

2RFS DSS Trk RFS/DSS RFS DSS Trk RFS/DSS Trk p 0.05 Trk mRNA TrkA, B, C

TrkA, B, C 2

TrkA, B, C (; p=0.022, p

- 3 -

RFS ( 2.294; 95% 1.309-4.032; p=0.004) DSS ( 2.146; 95% 1.195-3.861; p=0.011)

TRK1 ,2 ,3mRNA TrkA, B, C TrkA, C

TrkA RT-PCR TrkA TrkA TrkC Stage TrkB, C TrkA,B, C TrkA, C TrkB TrkA, C TrkB Zhang TrkB

TrkB TrkBZhang TrkB TrkB Stage Trk mRNA Trk

Trk VEGF Trk-TK/PI3K/Akt PI3K/Akt ERK/p38MAPK TrkA TrkA TrkC MMP-2, MMP-9 in vitroTrkBVEGF-AVEGF-C PI3K-Akt mTOR TrkC Trk

TrkA TrkA

( 1 )

5051

Tropomyosin-related kinaseTrkABC Trk ABC

Trk ABCTrk A

1. Trk ABC 2. Trk A 3 Trk A

Trk RT-PCRTrk

Trk A

( 2 )

- 1 -

High-fat diet increases vulnerability to atrial arrhythmia by conduction disturbance via miR-27b

HFDNC 2

optical mapping qRT-PCR mRNA/microRNA Western blotting Luciferase assay microRNA mRNA HL-1

HFD optical mapping HFD Cx40 miR-27b Luciferase assay miR-27b Cx40 mRNA 3UTR HL-1 miR-27b Cx40 miR-27b inhibitor Cx40

HFD miR-27b Cx40 atrial fibrillation: AF

AF AF --

- 2 -

action potential duration: APD AF microRNA AF AF

microRNA (C57BL/6) HFD NC 2 In vivo

ex vivo HEK293A HL-1

Electrophysiological study: EPS1-French His

di-4-ANEPPS CMOS APD Mallory-Azan microRNA totalRNA HL-1 cDNA

mRNA SYBR GreenmicroRNA TaqMan probe RT-PCR MicroRNA Array Cards 750 microRNA

HL-1 Western blotting 1 Cx40 GAPDH HRP 2

microRNA mRNA 3UTR miRTarBase TargetScan Luciferase 3'UTR microRNA HEK293A transfection Luciferase assay P NC HFD in vivo EPS HFD

Optical mapping HFD NC

APD90

- 3 -

IL-1IL-6Tnf- HFD Col1a3Col3a1Mmp2Mmp9Mallory-Azan Cx40 mRNA

HFD MicroRNA Array Cards microRNA HFD 14

microRNA Cx40 mRNA 3UTR microRNA miR-27b

HEK293ACx40 3UTRmiR-27b reporter vector miR-27b cotransfection miR-27b Cx40 3UTR HL-1

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HFD Cx40

HFD Cx40 microRNA HFD 14 microRNA miR-27b Cx40 3UTR

Luciferase assay miR-27b Cx40 3UTR 1 microRNA mRNA 3UTR Ppar-Dll4Spry2 miR-27b Ppar-Ppar-pioglitazone AF HFD

HFD HL-1

miR-27bCx40miR-27b

- 4 -

miR-27b Cx40

( 1 )

5052

Cx40 miR-27b

RNA

Cx40 RNA

miR-27b

RNA

.

- 1 -

Vessel Wall Inflammation of Takayasu Arteritis Detected by Contrast-Enhanced Magnetic Resonance Imaging: Association with Disease Distribution and Activity

MRI Late Gadolinium Enhancement: LGE

LGE Active

Inactive LGE LGE

LGE

MRI parameters

MRI

LGE

LGE

2011 3 2012 5 1.5TMRIAchieva Dual,Phillips Healthcare

49 MRI 2

Active 2 Inactive

Inactive

Active First-episode

Inactive

NIH criteriaActive/Inactive

LGE

- 2 -

MRI protocol

gadopentetate dimeglumine (Magnevist, Bayer) 0.15mmol/kg bolus LGE

sequence 30

LGE

Angiographic classification Type I V

Angiographic classification Type I V LGE classification

Region of interestROI Signal intensity(SI)

SIvessel SI

SIvessel 3 ROI SI SInoise

Standard deviationSD SDnoise

Signal-to-noise ratio (SNR) (= SIvessel / SDnoise) Contrast-to-noise ratio (CNR) (= (SIvessel -

SInoise) / SDnoise) pre-SNR, post-SNR, pre-CNR, post-CNR

SNR CNR SNR increment= post-SNR pre-SNR CNR increment(= post-CNR

pre-CNR) MRI parameters Active Inactive

Patient characteristics 19 Active 30 Inactive

CRPIndian Takayasus Arteritis Activity Score (ITAS)2010

First-episode 6

MRI parameters Active Inactive pre-SNR

(14.6 vs. 18.7; U = 238; P = 0.34), pre-CNR (11.2 vs. 12.4; U = 250; P = 0.47), post-SNR (48.7 vs. 45.5; U

= 284; P = 0.98), post-CNR (33.6 vs. 32.8; U = 252; P = 0.50), SNR increment (34.0 vs 24.6; U = 259; P =

0.59), or CNR increment (23.9 vs. 15.9; U = 221; P = 0.19)

First episode Inactive MRI parameters Active Inactive

: NIH criteria Active 13 Inactive 39

MRI parameters Active Inactive

LGE

- 3 -

LGE LGE

Sub-study NIH criteria MRI parameters

gadopentetate dimeglumine

Gadofosveset trisodiumintravascular contrast agentMRI

parameter Papa Reference number15

Negative study

MRI

( 1 )

5053

MRI MRI Late Gadolinium Enhancement: LGELGE LGE MRI parameters LGE

LGE

LGE

MRI

( 2 )

LGE F-18 FDG PET/CT LGE ROI

LGE

.

- 1 -

Semi-in-situ atomic force microscopy imaging of intracellular neurofilaments under physiological conditions through the sandwich method

SW13vim(-) neurofilament medium protein / -internexin

5060 nm

(NF)

NF-light (NF-L), NF-medium (NF-M), NF-heavy (NF-H) obligate heteropolymer NF

-internexin (-inx) NF NF NF

NF Heins NF-L 21 nm in vitro

- 2 -

(AFM)Mcke Brown NF 30-50 nm, 23 nm NF NF

NF

AFM

SW13vim(-) NF-M

-inx 12 mm NF

Alcian Blue

100 mM KCl, 3 mM MgCl2, 3 mM EGTA, 10 mM PIPES, pH 6.8

AM NanoWizard3 AFM system OMCL-AC160TN-R3 NF AFM Gwyddion

NF

EGFP NF-M NF AM-AFM (i) 3 nm 56 nm 50-60 nm (ii) 17 nm 220 nm (iii) 1.7 nm 28 nm 20-30 nm (i)(ii)NF (iii) NF

NF semi-in-situ

AFM NF NF

- 3 -

AFM AFM

(ii) NF NF (i) NF (i) 50-60 nm Mcke 30-50 nm

Heins Brown NF Ando vimentin 21-23 nm Mcke vimentin NF NF-M NF-H Hisanaga & Hirokawa NF NF-L Mcke AFM NF-L NF NF NF-M -inx NF

NF SW13vim(-) semi-in-situ AFM

NF AFM

50-60 nm NF

( 1 )

5054

3

AF-AFM Sw13Vim- NF-M -inx

AM-AFM

AM-AFM 3 3nm

( 2 )

56nm 50-60nm 17nm 220nm 1.7nm 28nm 20-30nm NF NF

. MDPhD 3 AFM

30

- 1 -

Expression of connective tissue growth factor in the livers of non-viral hepatocellular carcinoma patients with metabolic risk factors

connective tissue growth factor(CTGF) CTGF CTGF in vitro, in vivo CTGF CTGF CTGF CTGF

(HCC) 30 HCC

HCC IGF-1

DEN

connective tissue growth factor(CTGF)

- 2 -

CTGF CCN family CTGF 2006 2011 107

25 82 Hep3B, HLE, HuH7(THP-1) CTGF cDNA (ORIGENE ) Hep3B CTGF THP-1 PMA 48 Hep3B CTGF Hep3B(Hep3-CTGF)4, 8, 12, 24 THP-1 Hep3B, Hep3B-CTGF 6 4%PFA p65 NF-kB 5Hep3B, Hep3B-CTGF28 4m (DISCOVERY XT; Ventana) SPSS 20.0

BMI 90 DAVID Gene ontology cell adhesion regulation of cytoskeleton organization SLAMF7, CTGF, ITGBL1, LIMA1

- 3 -

CTGF in vitro CTGF Hep3B, HLE CTGFmRNA, CTGF CTGF HuH7 SLAMF7, ITGBL1, LIMA1 CTGF in vitro, in vivo CTGF Hep3B(Hep3B-CTGF)Hep3B In vitro Hep3B Hep3B-CTGF inflammatory response chemokine activity Hep3B, Hep3B-CTGF THP-1 CTGF Hep3B Hep3B-CTGF THP-1 CTGF NF-kB p65 Hep3B, Hep3B-CTGF 28 CTGF CTGF

CTGF CTGF CTGF CTGF (p=0.012), (p=0.035)p65(NF-kB)CTGF NF-kB (p=0.01)CTGF (DFS)(p=0.002)DFS CTGF CTGF DFS

CTGF In vitro, in vivo CTGF

CTGF CTGF

- 4 -

CTGF CTGF CTGF CTGF CTGF

CTGF CTGF CTGF

IL-6 CCL5

2 CTGF CTGF CTGF

CTGF CTGF CTGF

( 1 )

5055

connective tissue growth factor CTGFCTGF

1.CTGF2.CTGF

in vitro, in vivo

3.

CTGF4.CTGF

CTGF

CTGF

( 2 )

CTGF

.

- 1 -

Transplantation of autologous synovial mesenchymal stem cells promotes meniscus regeneration in aged primates

MSC

MSC 12 13 1/2 2.5105 MSC 14 Control 8 n=316 (n=4) MRI T1rho mapping MSC Control 816 modified Pauli Mankin 16 MSC Control T1rho 16 MSC Control MSC MSC

MSCMSCMSC10

- 2 -

MSC

2.5105

MSC 35l hanging drop 3 2 1 MSC 720 ( 14 ) Control 8n=316 (n=4) 16 MRI T1rho mapping 60cm2 500 14 Oil-Red O alizarin red

MSC Passage0 7 6 1.0106Passage1 Passage1 2.010625.5106 7.8106Passage0 Passage1 4.2 2.5 MSC hanging drop 3 2.5105mm

MSC Control 8 3MSC Control 16 4 MSC Control 8 MSC Safranin-O Control 16 MSC Safranin-O Control modified Pauli 8 3 16 4 MSC Control 16 T1rho 4 MSC Control 16 4 Mankin16 4 MSC Control Trho 4 MSC Control

- 3 -

MSCMSC 1/2 MSC

12 13 3 4 15 12 13 MSC MSC

MSC MSC MSC 3 1 MSC LacZ MSC 12 2 MSC OA MSC PRG4, BMP2, TSG-6 3 MSC 16 4 MSC Control 1 8 MSC Control MSC T1rho mapping T1rho mapping

T1rho Trho mapping 3 1 8 3 16 4 2 1/2

- 4 -

3 MSC

( 1 )

5056

1. MSC

MSC MSC MSC 2.

1

2

3

MSC

3.

MSC

( 2 )

MSC MSC

4.

5.

- 1 -

Michelle Loyola Nuylan

Down-regulation of LAPTM5 in human cancer cells

LAPTM5 (Lysosomal-associated protein multispanning transmembrane 5) gene is a

membrane protein on the intracellular vesicle that specifically regulates vesicle trafficking such as endocytosis. We previously found that this gene was transcriptionally down-regulated in cell lines and primary tumors of neuroblastoma (NB) by DNA methylation around its transcriptional start site. Interestingly, while LAPTM5 protein is constantly transported into lysosome for degradation, this protein is remarkably accumulated in NB cells occurring programmed cell death (PCD) within the tumors of favorable type, which frequently undergoes spontaneous regression. Furthermore, we have demonstrated that overexpression of LAPTM5 protein could induce lysosomal cell death due to lysosomal destabilization, as indicated by a leakage of cathepsin D from lysosomes into cytosol via lysosomal membrane permeabilization (LMP) and an impairment of autophagy degradation in NB cells. Additionally, the E3 ubiquitin ligase ITCH that is amplified in chromosome 20q of undifferentiated thyroid tumors, has oncogenic function, and could negatively regulate the expression level of LAPTM5 protein through proteasomal degradation via ubiquitination. The expression of ITCH protein also prevents LAPTM5-mediated cell death in NB cells. Thus, it has been suggested that the expression of LAPTM5 gene and the accumulation of its product contribute to the induction of PCD during tumor regression of NB and that LAPTM5 gene may function as a tumor suppressor in NB cells. However, the pathological expression and role of LAPTM5 in other types of human cancer are largely unknown. Here, we report that expression of LAPTM5 gene is frequently down-regulated at the

transcriptional level in various types of human cancer cell lines and in tumor cases of non-small cell lung cancer (NSCLC) and esophageal squamous cell carcinoma (ESCC), and its down-regulation is associated with poor prognosis of patients with ESCC and NSCLC. Importantly, we showed that overexpression of this protein could induce lysosomal cell death in KYSE170 cells, an ESCC cell line, as well as in NB cells. These findings suggest that inactivation of LAPTM5 gene may contribute to tumorigenesis in a subset of human cancers.

- 2 -

Lysosomal-associated protein multispanning transmembrane 5 (LAPTM5)LAPTM5 Neuroblastoma; NBNB LAPTM5 mRNA qRT-PCR LAPTM5 mRNA LAPTM5 338 LAPTM5 mRNA qRT-PCR 315 93.2%LAPTM5 mRNA 32 12 LAPTM5 mRNA Oncomine PrognoScanLAPTM5 mRNA KYSE170KYSE150H460 LAPTM5 LAPTM5 D LAPTM5

( 1 )

5057 Michelle Loyola Nuylan

LAPTM5 LAPTM5

LAPTM5 (Neuroblastoma;NB)

1.18 18 LAPTM5 mRNA LAPTM5mRNA

2.LAPTM5 LAPTM5

LAPTM5

LAPTM5

( 2 )

.

- 1 -

Ipragliflozin improves hepatic steatosis in obese mice and liver dysfunction in type 2 diabetic patients irrespective of body weight reduction

2 NAFLD, non-alcoholic fatty liver diseaseSodium-glucose cotransporter 2SGLT2 SGLT2

ob/ob SGLT2

2 24 NAFLD 2 SGLT2 2 NAFLD, non-alcoholic fatty liver diseaseNASH, non-alcoholic steatohepatitis2 NAFLD 2 NASH

Sodium-glucose cotransporter 2SGLT2

- 2 -

90%SGLT2

SGLT2

2 SGLT2 SGLT2 2 SGLT2 8 C57BL/6J 16 4 SGLT2 10mg/kg vehicle 16 4 vehicle

Akt 7 C57BL/6J-ob/ob 4 10mg/kg vehicle BMI 22kg/m2

HbA1c 6.5% 2 55 50mg 24 HbA1c C57BL/6J 16

vehicle ALT vehicle C57BL/6J-ob/ob

4 3-Srebp1c Fasn vehicle F4/80 crown-like structure F4/80Tnf Adipoq Vehicle

- 3 -

2 55 48 24 24 75.42.173.02.1kg 151.36.1125.53.8mg/dlHbA1c 7.70.27.30.1% ALT 41.84.528.32.0 IU/l -GTP 48.25.939.35.1IU/l 20% 1%48 3 3 3 24 ALT 3 ALT

SGLT2 2 SGLT2

12

crown-like structure

phosphatase and tensin homologue PTEN

2 NAFLD SGLT2

- 4 -

NAFLD 2 SGLT2

( 1 )

5058

1

ipragliflozin 2

Ipragliflozin Na-glucose cotranspoter SGLT-II

(ob/ob mouse)

3

( 2 )

4

- 1 -

Joint capsule attachment to the coronoid process of the ulna: an anatomic study with implications regarding the type 1 fractures of the coronoid process of the ODriscoll classification

ODriscoll Type1 2mm Subtype1 2mm

Subtype2 Subtype1

17 10

5

2 11.96.1 1.94.7 0.59mm, 0.34mm 2.63mm, 1.69mm ODriscoll Subtype2

Regan X

Type1 Type2

- 2 -

ODriscoll CT 3 2 Subtype12 Subtype2 Subtype

Subtype1 2

17 8 9 77 10

5

2 5 2 2

1A

1B

()() 2A

2B 5.8

- 3 -

6.1 11.9 32 0.59mm0.34mm 2.63mm1.69mm 0.48mm0.27mm 1.33mm1.76mm ODriscoll Type1 ODriscoll Type1 Subtype1 2 4.7 4 1.9mm 0.8 0.860.98

Cage 6.4mm Regan Type 5.8Cage Ablove 2.36Regan TypeAblove

ODriscoll Type1 Subtype1 2mm

Subtype2 2mm Subtype1 Subtype 2

1.9 2ODriscoll Type1 Subtype 2

- 4 -

ODriscoll Subtype1 2

ODriscoll 50

1.9ODriscoll Subype2

( 1 )

5059

ODriscollType1

ODriscoll Type1 2mm Subtype1 2mm

Subtype2 Subtype1

ODriscoll 17 10

5 2

11.9 6.1 1.94.7ODriscoll Subtype2

( 2 )

.

- 1 -

A functional SNP in FLT1 increases risk of coronary artery disease in a Japanese population

(Coronary artery disease: CAD)CAD

(GWAS) CAD 15 SNP SNP CAD Fms 1 FLT1 (rs9319428)(P=5.9810-8)FLT1 tag SNPs CAD SNP (rs74412485) SNP FLT1 1 FLT1 RNAi FLT1 FLT1 SNP FLT1 CAD CAD CAD 40-50% CAD CAD CAD GWAS CAD GWAS CAD SNP CADFLT1 SNPFLT1 CAD in vitro

- 2 -

7,990 CAD 6,582 DNA Illumina OmniExpress BeadChip PCR invader assay

15 SNP 1 0.0033 (0.05/15)Genetic Power Calculator ( 0.2 0.0033(0.05/15))SNP-SNP PLINK 1.07

FLT1 0.05 74 tag SNP Haploview software 1000 10 SNP PCR 2,861 CAD 2,066 51 SNP (10 SNP 3 SNP ) rs9319428 P 15 SNP DNA CAD pGL3 basic vector FLT1

H3K27Ac 3 SNP (rs74412485) 25

RNAi FLT1 short interference (si) RNA RNA cDNA SELE, ICAM, VCAM mRNA FLT1 CD31 ()

FLT1 CAD SNP (rs9319427, P=5.9810-8)EDNRA SNP (rs6842241, P=0.000207) FURIN SNP (rs17514846, P=0.00311) CAD CAD genotype (P>0.05)SNP-SNP FLT1 SNP (rs9319428) CAD 15 SNP 15 SNP SNP (rs74412485, P=2.8510-12) CAD SNP (rs74412485) SNP FLT1 CAD rs74412485rs9319428rs2387632 3

- 3 -

SNP 1.7 RNAi FLT1 siRNA FLT1 SELEICAM1VCAM FLT1 FLT1 CD31 FLT1 CAD FLT1 CAD FLT1 vascular endothelial growth factor receptor (VEGFR)family VEGF FLT1 FLK1 endothelial regression FLT1 FLT1 selectin-E, ICAM1, VCAM CAD FLT1 Selectin-EICAM1VCAM CAD CAD EDNRA endothelin-1 Endothelin-1

CAD FURIN proprotein convertase subtilisin/kexin

(PCSK)FURIN PCSK9 CAD PCSK9 LDL 1 PCSK9 LDL FURIN CAD

CAD SNP CAD FLT1 SNP SNP FLT1 CAD

( 1 )

5060

1. FLT1 SNP

2. 1

GWAS SNP

FLT1

SNP

2

FLT1

FLT1

3

GWAS 15 SNP

:7,990 6,582

FLT1 64 tag SNP

rs74412485 rs74412485 FLT1

SNP FLT1

4

FLT1

3.

- 1 -

Monoiodoacetic acid induces arthritis and synovitis in rats in a doseand time-dependent manner: proposed model-specific scoring systems

monoiodoacetic acidMIA1

3 Wistar MIA OARSI score MIA

46 4 0.1mg 0.2mg 2 0.2mg 12 0.5mg 1mg 4 5 14 MIA

MIA MIA

OAOA

OA monoiodoacetic acidMIA13 MIA MIA

- 2 -

MIA MIA OA

IFP MIA IFP

Wistar 8 MIA(0.1mg0.2mg0.5mg1mg/50l) PBS 50l n = 4 246812 MIA O OARSI score Wistar Rat8 MIA(0.2mg1mg/50l) PBS 50l n = 4 135714 HE(IFP) 0.1mg 4 48

12 0.2mg 4 46 8 12 0.5mg 2 4 1mg 2 4 0.1mg 4 0.750.43 0.2mg 2 1.250.43 8 0.5mg 1mg 4 0.1mg 0.2mg 2

0.2mg 12 0.5mg 1mg 4 OARSI score 0.1mg 4 3.52.9 0.2mg 2 5.53.2 8 0.5mg 2 191.7 1mg 2 202.84 Mankin

IFP 0.2mg 3 5 7 IFP IFP 1mg 3 5 0.2mgIFP 14

- 3 -

0.2mg 5 1mg 14 46

4 MIA MIA

MIA 0.1mg O Wistar MIA MohanThote MIA Guingamp Ferreira-Gomes Bove MIA MIA MIASprague-Dawley MIA Wistar

MIA MIA MIA MIA Guingamp

0.1mm MIA IFP OA

0.2mg 5 1mg 14 0.2mgMIA 1mgMIA IFP IFP

MIA MIA

MIA 0.2mg 1mg MIA MIA

( 1 )

5061

7-800

Wistar

1/51/10

.

- 1 -

Loxoprofen sodium induces the production of complement C5a in human serum

(BAT) IgE

(COX) (NSAID) BAT 1530 24

24 24

24

C5a in vitro C5a

C5a 300 g/mL Cmax 5.04 g/mL

BAT IgE IgE CD203c CD63 NSAID

2011

- 2 -

BAT 30 24 24

24

BAT Allergenecity kit (Beckman coulter)

50L50 LPC7CD3FITCCD294PECD203c 10 L 37 CD203c 1 30

1 80 mL PBS 1:4 37 24 BAT A 2 PBS

C5a ELISA (Hycult Biotech) C5a (CD88)

C5a W54011 (Merck Millipore) BAT 30

24 CD203c 24 30 24 BAT

24

- 3 -

20 A

2 PBS () C5a C5a C5a 24 C5a 24

C5a COX

COX COX C5a C3a COX C5aC5a

C5a C5a

C5a C5a BAT C5a

C5a

( 1 )

5062

BAT BAT IgE

BAT

C5a BAT

BAT

- 1 -

Recovery of renal function after radical nephrectomy and risk factors for postoperative severe renal impairment: A Japanese multicenter longitudinal study

10

1-2% 10

JA

1994 2011 1033 (58 )(60 )(3 )(211 ) 701 423 278

10

- 2 -

10

65 60 mL/min/1.73 m2

(mL/min/1.73 m2) = 194 (mg/dl)-1.094 -0.287 0.739 ().

5050

50% 50%

701 469

64 23.4kg/m269.6mL//1.78m24.1cm 25.4%42.8%15.2%15.8% 62 9 1.3% 76 20 45.7 mL/min/1.73 m2 10

51.3 mL/min/1.73 m20.34 mL/min/1.73 m2 (95% : 0.17 0.50)

65 50% 58

50%

50 50%5 96.5%90.4%75.6%

- 3 -

50%

50%

2.67

50% 58 34.5%70.7% 65 50%65 304 11 3.6%65 59 14 23.7%

50%

60 mL/min/1.73 m2

- 4 -

50%

( 1 )

5063

10

1.

10

2.

65

IC

.

- 1 -

Womens Preference for a Male Acquaintance Enhances Social Reward Processing of Material Goods in the Anterior Cingulate Cortex

functional magnetic resonance imaging: fMRIi 2 ii

2 12

32

3 12

3

- 2 -

1)

2)

fMRI

3,4)

iii 2 : 1705: N24-427 19.81 1.14 fMRI 2

9 fMRI 7 20 31 19.90 1.33 30

9 5 2 2 4 iii

- 3 -

SPSS MRI SPM8 p < 0.001 (uncorrected) p < 0.05 (FWE corrected)psycho-physiological interaction (PPI) p < 0.001 (uncorrected) 80 3 1 (F(1, 38) = 458.50, p < 0.001)2 (Bonferroni corrected p < 0.001)

3

3 1

5,6) 2

7) 3

8)

9)

( 1 )

5064

functional magnetic resonance imaging: fMRI

fMRI

12 3 4

( 2 )

.

- 1 -

Circadian Clock Regulates Bone Resorption in Mice

Abstract The circadian clock controls many behavioral and physiological processes beyond daily

rhythms. Circadian dysfunction increases the risk of cancer, obesity, and cardiovascular and metabolic diseases. Although clinical studies have shown that bone resorption is controlled by circadian rhythm, as indicated by diurnal variations in bone resorption, the molecular mechanism of circadian clockdependent bone resorption remains unknown. To clarify the role of circadian rhythm in bone resorption, aryl hydrocarbon receptor nuclear translocator-like (Bmal1), a prototype circadian gene, was knocked out specifically in osteoclasts. Osteoclast-specific Bmal1-knockout mice showed a high bone mass phenotype due to reduced osteoclast differentiation. A cell-based assay revealed that BMAL1 upregulated nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1 (Nfatc1) transcription through its binding to an E-box element located on the Nfatc1 promoter in cooperation with circadian locomotor output cycles kaput (CLOCK), a heterodimer partner of BMAL1. Moreover, steroid receptor coactivator (SRC) family members were shown to interact with and upregulate BMAL1:CLOCK transcriptional activity. Collectively, these data suggest that bone resorption is controlled by osteoclastic BMAL1 through interactions with the SRC family and binding to the Nfatc1 promoter. Introduction Bone remodeling, which is affected in most bone metabolic disorders, such as osteoporosis,

mainly comprises two phases: bone resorption by osteoclasts and bone formation by osteoblasts. Bone resorption and bone formation occur in a balanced manner to maintain constant bone mass. The circadian clock controls daily rhythms to adapt to a 24-hour day-night periodicity and

thereby controls many behavioral and physiological processes. Indeed, disruptions to the circadian clock cause abnormal daily rhythms, which leads to various metabolic diseases,

- 2 -

including obesity, hypertension, and osteoporosis. In mammals, the central clock is located in the suprachiasmatic nucleus (SCN) in the brain,

whereas the peripheral clock is located in most other tissues. The central clock has long been considered to synchronize and control the peripheral clock through neuronal and hormonal pathways. In contrast, the peripheral clock has been viewed as a dependent mechanism, simply working to maintain whole-body daily rhythm in cooperation with the central clock. However, this belief was challenged when the tissue-specific function of aryl hydrocarbon receptor nuclear translocator-like (Bmal1) was discovered, suggesting that the peripheral clock, especially peripheral BMAL1 may have its own role in peripheral tissues independent of the central clock. The central clock and the peripheral clock share a common molecular mechanism and

comprise an autoregulatory transcriptional-translational feedback loop. The classical clock machinery comprises two positive elements, BMAL1 and circadian locomotor output cycles kaput (CLOCK), and two negative elements, period circadian clock (PER1, PER2, and PER3) and cryptochrome (photolyase-like) (CRY1 and CRY2). Generally, the heterodimeric transcription factor BMAL1:CLOCK activates the transcription of circadian-related genes, such as Per and Cry, by binding to the CACGTG-type (or CACGTT-type-like) E-box elements in their promoters. In turn, PER and CRY form a multimeric complex and then inhibit the transcriptional activity of BMAL1:CLOCK. These positive and negative feedback loops have been shown to be involved in many processes, such as aging, adipogenesis, cancer, energy homeostasis, and endochondral ossification. Although the circadian clock mediates the action of leptin in bone formation, its function in bone resorption has not been clearly elucidated. In this study, we generated osteoclast-specific Bmal1-knockout mice to investigate the

involvement of the circadianclock in the mechanisms underlying the regulation of bone resorption and in the interaction between SRCs and the BMAL1:CLOCK heterodimer. Subjects and Methods Transgenic mice expressing Cre-recombinase under the control of the cathepsin K promoter

(Ctsk-Cre mice) and nestin promoter (Nes-Cre mice) were mated with floxed Bmal1 mice (Bmal1f/f) mice to obtain the conditional knockout mice. We constructed reporter plasmids and did dual-luciferase reporter assay. We did southern blot analysis to assess the efficiency of recombination using osteoclast and brain genomic DNA. We injected mice with calcein i.p. 5 days and 2 days prior to euthanasia and stained the

undecalcified sections of the third and fourth lumbar vertebrae using Von Kossa and tartrate-resistant acid phosphatase (TRAP) staining. We performed static and dynamic histomorphometric analysis using the OsteoMeasure Analysis System. We obtained two-dimensional images of the distal femurs by microcomputed tomography analysis. We cultured osteoclast from bone marrow cells in -MEM supplemented with 10% FBS in

- 3 -

the presence of human macrophage colony-stimulating factor and human RANKL. RNAs and proteins were harvested and analyzed by quantitative RT-PCR analysis and Western blot. Results Bmal1osc/ mice show high bone mass through the reduction of the osteoclast number. The

absence of Bmal1 in osteoclasts leads to high bone mass in Bmal1osc/ mice without overtly affecting calcium metabolism and the RANKL/OPG system. BMAL1 regulates bone remodeling independent of the central clock. osteoclast markers, acid phosphatase 5, tartrate resistant (Acp5) and Nfatc1, their rhythmic expression in bone was dampened in the Bmal1osc/ mice. BMAL1 regulates Nfatc1 expression in the osteoclast in corporation of CLOCK. BMAL1:CLOCK heterodimeric complex binds to the E-box element in the Nfatc1 promoter to activate Nfatc1 expression. SRCs interacted with the BMAL1:CLOCK complex to synergistically activate Nfatc1 transcription. Discussion Studies have shown that the peripheral clock is not strictly controlled by the central clock.

Some investigations indicate that the peripheral clock regulates the rhythmic expression of genes in local tissues independent of central clock control. Recently, BMAL1 has been shown to possess tissue-specific functions. In this study, we showed that osteoclast-specific Bmal1-knockout mice displayed higher bone mass, whereas neuron-specific Bmal1-knockout mice displayed normal bone mass. The global Bmal1-knockout mice showed lower bone mass due to increased bone formation

and bone resorption. Furthermore, they showed a bone phenotype similar to the osteoblast-specific Bmal1-knockout mice. We believed that BMAL1 inhibited bone resorption through the repression of Rankl expression in osteoblasts. In this study, we showed that bone resorption was repressed in osteoclast-specific Bmal1-knockout mice. These results demonstrate that Bmal1 regulates bone resorption through two different mechanisms: indirect inhibition by osteoblasts and direct stimulation by osteoclasts. Apart from regulating circadian rhythm, the BMAL1:CLOCK heterodimer regulates genes

expression as a transcription factor. In the present study, osteoclast-specific Bmal1-knockout mice demonstrated abnormal rhythms and decreased expression of Nfatc1 without overt alterations in the expression of circadian genes. Thus, independent of its effect on circadian regulation, BMAL1 likely regulates bone resorption as a transcription factor; ie, BMAL1 alone increases bone resorption via Nfatc1 induction in osteoclasts or decreases resorption via the inhibition of RANKL in osteoclasts as a transcription factor. Bone resorption has a diurnal rhythm. In this work, we demonstrated that BMAL1:CLOCK

directly activates Nfatc1 transcription by binding to the E-box in its promoter. NFATC1 directly and indirectly regulates the expression of bone resorption-related genes, as Ctsk,

- 4 -

carbonic anhydrase 2 (Car2), interleukin-2 (IL-2), demonstrating rhythmic expression patterns. Together, these results indicate that BMAL1:CLOCK may regulate rhythmic bone resorption through the activation of Nfatc1. Moreover, it has been demonstrated that SRC-2 expression displays rhythmicity and interacts with BMAL1:CLOCK in the liver. In this study, SRC expression levels decreased in the bones of osteoclast-specific Bmal1-knockout mice. Moreover, SRCs, as coactivators of BMAL1:CLOCK, amplified Nfatc1 transcription. These results clearly demonstrate that SRCs are regulated by BMAL1, and BMAL1 and SRCs synergistically affect bone resorption. Conclusion BMAL1 in osteoclasts regulated bone resorption through the regulation of Nfact1

transcription in cooperation with SRCs.

Bmal1Bmal1BMAL1:CLOCK heterodimerNfatc1E-box(-5281bp)Nfatc1P160(SRCs)BMAL1SRCs