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Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity

Bone Research 2024年第1期12卷 180-198页

作者： Morten S.Hansen Kaja Madsen Maria Price Kent Søe yasunori omata Mario M.Zaiss Caroline M.Gorvin Morten Frost Alexander Rauch Molecular Endocrinology Laboratory(KMEB) Department of EndocrinologyOdense University HospitalDK-5000 Odense CDenmark Department of Clinical Research Faculty of Health SciencesUniversity of Southern DenmarkDK-5000 Odense CDenmark Clinical Cell Biology Pathology Research UnitDepartment of Clinical ResearchUniversity of Southern DenmarkDK-5000 Odense CDenmark Institute of Metabolism and Systems Research(IMSR)and Centre for Diabetes Endocrinology and Metabolism(CEDAM)University of BirminghamBirmingham B152TTUK Centre for Membrane Proteins and Receptors(COMPARE) Universities of Birmingham and NottinghamBirmingham B152TTUK Department of Molecular Medicine University of Southern DenmarkDK-5000 Odense CDenmark Department of Orthopedic Surgery Faculty of MedicineThe University of TokyoTokyo 113-8655Japan Department of Internal Medicine 3 Rheumatology and ImmunologyFriedrich-Alexander-University Erlangen-Nürnberg(FAU)and Universitätsklinikum ErlangenD-91054 ErlangenGermany Deutsches Zentrum Immuntherapie(DZI) Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum ErlangenD-91054 ErlangenGermany Steno Diabetes Center Odense Odense University HospitalDK-5000 Odense CDenmark

Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone *** novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment *** study aimed to provide an overview of transcriptional reprogramming during human osteoclast *** were differentiated from CD14+monocytes from eight female *** sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across *** patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density *** analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional *** donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature *** expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and *** regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating SSTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature *** conclus

关键词： osteoclast programming identif

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Caspase-8 promotes scramblase-mediated phosphatidylserine exposure and fusion of osteoclast precursors

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Bone Research 2024年第3期12卷 611-620页

作者： Brenda Krishnacoumar Martin Stenzel Hilal Garibagaoglu yasunori omata Rachel L.Sworn Thea Hofmann Natacha Ipseiz Magdalena A.Czubala Ulrike Steffen Antonio Maccataio Cornelia Stoll Christina Böhm Martin Herrmann Stefan Uderhardt Robert H.Jenkins Philip R.Taylor Anika Grüneboom Mario M.Zaiss Georg Schett Gerhard Krönke Carina Scholtysek Department of Internal Medicine 3-Rheumatology and Immunology Friedrich-Alexander University Erlangen-Nürnberg(FAU)and Universitätsklinikum Erlangen91054 ErlangenGermany Deutsches Zentrum für Immuntherapie(DZI) Friedrich-Alexander University Erlangen-Nürnberg(FAU)and Universitätsklinikum Erlangen91054 ErlangenGermany Department of Biopsectroscopy Leibniz Institut für Analytische Wissenschaften-ISAS-e.V.Bunsen-Kirchhoff-Str.11Dortmund 44227Germany Medical Faculty University HospitalUniversity Duisburg-EssenEssen 45147Germany Systems Immunity Research Institute Heath ParkCardiff UniversityCardiff CF144XNUK Optical Imaging Competence Centre(FAU OICE) Exploratory Research UnitFriedrich-Alexander University Erlangen-Nürnberg(FAU)ErlangenGermany Division of Infection&Immunity Heath ParkCardiff UniversityCardiff CF144XNUK Deutsches Rheuma-Forschungszentrum Berlin BerlinGermany Department of Rheumatology and Clinical Immunology Charité-Universitätsmedizin BerlinBerlinGermany

Efficient cellular fusion of mononuclear precursors is the prerequisite for the generation of fully functional multinucleated bone-resorbing ***,the exact molecular factors and mechanisms controlling osteoclast fusion remain incompletely *** we identify RANKL-mediated activation of caspase-8 as early key event during osteoclast fusion.

关键词： incomplete exact activation

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Review of dynamic contrast-enhanced ultrasound guidance in ablation therapy for hepatocellular carcinoma

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World Journal of Gastroenterology 2011年第45期17卷 4952-4959页

作者： yasunori Minami Masatoshi Kudo Department of Gastroen-terology and Hepatology Kinki University School of Medicine

Local ablative techniques-percutaneous ethanol injection, microwave coagulation therapy and radiofrequency ablation (RFA)-have been developed to treat unresectable hepatocellular carcinoma (HCC). The success rate of percutaneous ablation therapy for HCC depends on correct targeting of the tumor via an imaging technique. However, probe insertion often is not completely accurate for small HCC nodules, which are poorly def ined on conventional B-mode ultrasound (US) alone. Thus, multiple sessions of ablation therapy are frequently required in diffi cult cases. By means of two breakthroughs in US technology, harmonic imaging and the development of second-generation contrast agents, dynamic contrast-enhanced harmonic US imaging with an intravenous contrast agent can depict tumor vascularity sensitively and accurately, and is able to evaluate small hypervascular HCCs even when B-mode US cannot adequately characterize the tumors. Therefore, dynamic contrast-enhanced US can facilitate RFA electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of dynamic contrast-enhanced US guidance in ablation therapy for liver cancer is an effi cient approach. Here, we present an overview of the current status of dynamic contrast-enhanced US-guided ablation therapy, and summarize the current indications and outcomes of reported clinical use in comparison with that of other modalities.

关键词： Dynamic contrast-enhanced ultrasound Hepatocellular carcinoma Percutaneous ethanol injection Radiofrequency ablation

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Interaction between hepatitis C virus and metabolic factors

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World Journal of Gastroenterology 2014年第11期20卷 2888-2901页

作者： yasunori Kawaguchi Toshihiko Mizuta Department of Internal Medicine Saga Medical SchoolSaga 849-8501Japan

Hepatitis C virus (HCV) infection disrupts the normal metabolism processes, but is also influenced by several of the host’s metabolic factors. An obvious and significantly detrimental pathophysiological feature of HCV infection is insulin resistance in hepatic and peripheral tissues. Substantial research efforts have been put forth recently to elucidate the molecular mechanism of HCV-induced insulin resistance, and several cytokines, such as tumor necrosis factor-α, have been identified as important contributors to the development of insulin resistance in the distant peripheral tissues of HCV-infected patients and animal models. The demonstrated etiologies of HCV-induced whole-body insulin resistance include oxidative stress, lipid metabolism abnormalities, hepatic steatosis and iron overload. In addition, myriad effects of this condition have been characterized, including glucose intolerance, resistance to antiviral therapy, progression of hepatic fibrosis, development of hepatocellular carcinoma, and general decrease in quality of life. Metabolic-related conditions and disorders, such as visceral obesity and diabetes mellitus, have been shown to synergistically enhance HCV-induced metabolic disturbance, and are associated with worse prognosis. Yet, the molecular interactions between HCV-induced metabolic disturbance and host-associated metabolic factors remain largely unknown. The diet and lifestyle recommendations for chronic hepatitis C are basically the same as those for obesity, diabetes, and metabolic syndrome. Specifically, patients are suggested to restrict their dietary iron intake, abstain from alcohol and tobacco, and increase their intake of green tea and coffee (to attain the beneficial effects of caffeine and polyphenols). While successful clinical management of HCV-infected patients with metabolic disorders has also been achieved with some anti-diabetic (i.e., metformin) and anti-lipid (i.e., statins) medications, it is recommended th

关键词： Hepatitis C virus Insulin resistance Diabetes Lipid metabolism abnormality Hepatic steatosis Iron overload Oxidative stress Visceral obesity

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Distortion-free PCA on sample space for highly variable gene detection from single-cell RNA-seq data

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Frontiers of Computer Science 2023年第1期17卷 133-142页

作者： Momo MATSUDA yasunori FUTAMURA Xiucai YE Tetsuya SAKURAI Department of Computer Science University of TsukubaTsukuba 305-8573Japan

Single-cell RNA-seq (scRNA-seq) allows the analysis of gene expression in each cell, which enables the detection of highly variable genes (HVG) that contribute to cell-to-cell variation within a homogeneous cell population. HVG detection is necessary for clustering analysis to improve the clustering result. scRNA-seq includes some genes that are expressed with a certain probability in all cells which make the cells indistinguishable. These genes are referred to as background noise. To remove the background noise and select the informative genes for clustering analysis, in this paper, we propose an effective HVG detection method based on principal component analysis (PCA). The proposed method utilizes PCA to evaluate the genes (features) on the sample space. The distortion-free principal components are selected to calculate the distance from the origin to gene as the weight of each gene. The genes that have the greatest distances to the origin are selected for clustering analysis. Experimental results on both synthetic and gene expression datasets show that the proposed method not only removes the background noise to select the informative genes for clustering analysis, but also outperforms the existing HVG detection methods.

关键词： single-cell RNA-sequencing feature selection principal component analysis highly variable gene detection background noise clustering analysis

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Therapeutic response assessment of RFA for HCC:Contrast-enhanced US,CT and MRI

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World Journal of Gastroenterology 2014年第15期20卷 4160-4166页

作者： yasunori Minami Naoshi Nishida Masatoshi Kudo Department of Gastroenterology and Hepatology Kinki University Faculty of MedicineOsaka 589-8511Japan

Radiofrequency ablation (RFA) is commonly applied for the treatment of hepatocellular carcinoma (HCC) because of the facile procedure, and the safety and effectiveness for the treatment of this type of tumor. On the other hand, it is believed that HCC cells should spread predominantly through the blood flow of the portal vein, which could lead to the formation of intrahepatic micrometastases. Therefore, monitoring tumor response after the treatment is quite important and accurate assessment of treatment response is critical to obtain the most favorable outcome after the RFA. Indeed, several reports suggested that even small HCCs of ≤ 3 cm in diameter might carry intrahepatic micrometastases and/or microvascular invasion. From this point of view, for preventing local recurrences, RFA should be performed ablating a main tumor as well as its surrounding non-tumorous liver tissue where micrometastases and microvascular invasion might exist. Recent advancement of imaging modalities such as contrast-enhanced ultrasonic, computed tomography, and magnetic resonance imaging are playing an important role on assessing the therapeutic effects of RFA. The local recurrence rate tends to be low in HCC patients who were proven to have adequate ablation margin after RFA; namely, not only disappearance of vascular enhancement of main tumor, but also an adequate ablation margin. Therefore, contrast enhancement gives important findings for the diagnosis of recurrent HCCs on each imaging. However, hyperemia of non-tumorous liver surrounding the ablated lesion, which could be attributed to an inflammation after RFA, may well obscure the findings of local recurrence of HCCs after RFA. Therefore, we need to carefully address to these imaging findings given the fact that diagnostic difficulties of local recurrence of HCC. Here, we give an overview of the current status of the imaging assessment of HCC response to RFA.

关键词： Hepatocellular carcinoma Micrometastasis Microvascular invasion Radiofrequency ablation Safety margin

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Topographical and hydrological effects on meso-scale vegetation in desert steppe, Mongolia

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Journal of Arid Land 2017年第1期9卷 132-142页

作者： Batdelger GANTSETSEG Masahide ISHIZUKA yasunori KUROSAKI Masao MIKAMI Information and Research Institute of Meteorology Hydrology and Environment Ulaanbaatar 15160 Mongolia Faculty of Engineering Kagawa University Takamatsu 761-03 96 Japan Arid Land Research Center Tottori University Tottori 680-0001 Japan Japan Meteorological Business Support Center Tokyo 101-0054 Japan

This study investigated the seasonal variations of the normalized difference vegetation index（NDVI） and its relationships with climatic variables and topography in a small-scale（20 km×20 km） area（i.e., Tsogt-Ovoo village） within the desert steppe zone of Mongolia using in-situ observed climate data and satellite remote sensing data. We found that the topography is very important for vegetation growth in the desert steppe although the summer precipitation is the constraining factor. The unexpectedly high NDVI（up to 0.56）, as well as the high aboveground biomass, in the valley bottom was primarily resulted from the topography-modulated redistribution of overland flow after relatively heavy precipitation events during the growing season. This makes the valley bottoms in desert steppes not only reliable feeding resources for livestock but also heavens for wild lives. But, the detected large standard deviation of annual maximum NDVI（NDVI_（max）） from 2000 to 2013 in the valley bottom in response to rather variable precipitation implies that the valley bottoms under desert steppe climates are more vulnerable to climatic change.

关键词： topography climatic variable desert valley vegetation soil moisture Terra-MODIS NDVI

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Contrast-enhanced ultrasonography with Sonazoid in hepatocellular carcinoma diagnosis

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Hepatoma Research 2020年第8期6卷 1-11页

作者： yasunori Minami Masatoshi Kudo Department of Gastroenterology and Hepatology Kindai University Faculty of MedicineOsaka 589-8511Japan.

With the development of second-generation contrast agents and advancement in contrast harmonic imaging,contrast-enhanced ultrasonography(CEUS)now has the capacity to sensitively and accurately show tumor ***,marked improvements have been achieved in the diagnosis of focal liver lesions(FLLs),including hepatocellular carcinoma(HCC),by *** contrast to other agents,Kupffer cells in liver sinusoids take up *** contrast enhancement phases occur in CEUS with Sonazoid:a vascular phase and Kupffer *** obtained in the Kupffer phase have higher diagnostic sensitivity for hepatic malignancies because the majority of these malignancies do not contain Kupffer *** images obtained in the vascular phase markedly narrow the clinical differential diagnoses of *** sustainable detection of inconspicuous HCC,adequate guidance of ablation therapy,and accurate assessment of treatment responses in HCC are all facilitated by *** principles,clinical applications,and techniques of CEUS with Sonazoid in the diagnosis of HCC will be reviewed herein.

关键词： Contrast-enhanced ultrasonography focal liver lesion hepatocellular carcinoma sonazoid

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Adjuvant therapy after radical surgery for hepatocellular carcinoma: still an unmet need

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Hepatobiliary Surgery and Nutrition 2019年第4期8卷 414-416页

作者： yasunori Minami Masatoshi Kudo Department of Gastroenterology and Hepatology Kindai University Faculty of Medicine Osaka-Sayama Osaka Japan

Introduction Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related *** HCC typically occurs in patients with advanced liver disease,therapeutic decisions depend on the degree of underlying liver dysfunction and tumor *** treatment options,which result in 5-year survival rates of 60–80%(surgical resection)and 40–70%(local ablative therapies),are restricted to patients with early-stage HCC(1,2).However,surgical resection and local ablative therapies are limited by high tumor recurrence rates of 50%at 3 years and 70%at 5 years(1-6).Thus,monitoring treatment response is imperative for the clinical management of HCC patients(7),highlighting the need for adjuvant therapies.

关键词： mortality surgery clinical

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Carcinoma ex pleomorphic adenoma of the sublingual gland:a case report

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International Journal of Oral Science 2012年第1期4卷 50-53页

作者： yasunori Ariyoshi Masashi Shimahara Toshiyuki Konda Motomu Tsuji Department of Dentistry and Oral Surgery Division of Medicine for Function and Morphology of Sensory OrgansOsaka Medical CollegeTakatsukiJapan Department of Surgical Pathology Osaka Medical College HospitalTakatsukiJapan

We report a case of carcinoma ex pleomorphic adenoma of a sublingual gland in a 70-year-old *** a clinical diagnosis of benign salivary gland tumor,excision of the mass with the sublingual salivary gland in an en bloc fashion via an intraoral approach was ***,there was a rupture of the fibrous capsule and diffuse cell-rich sheets composed of myoepithelial cells with round nuclei were also ***,the cells that composed of cell rich sheets were positive to smooth muscle *** diagnosis of myoepithelial carcinoma ex pleomorphic adenoma was made.

关键词： Pleomorphic adenoma malignant myoepithelial carcinoma sublingual gland magnetic resonance imaging

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