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Crosstalk between CYP2E1 and PPARα substrates and agonists modulate adipose browning and obesity

Acta Pharmaceutica Sinica B 2022年第5期12卷 2224-2238页

作者： Youbo Zhang Tingting Yan Tianxia Wang Xiaoyan Liu Keisuke Hamada Dongxue Sun Yizheng Sun Yanfang Yang Jing Wang Shogo takahashi Qiong Wang Kristopher W.Krausz Changtao Jiang Cen Xie Xiuwei Yang Frank J.Gonzalez State Key Laboratory of Natural and Biomimetic Drugs and Department of Natural Medicines School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Laboratory of Metabolism Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA School of Life Science and Engineering Lanzhou University of TechnologyLanzhou 730050China Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking Universitythe Key Laboratory of Molecular Cardiovascular ScienceMinistry of EducationBeijing 100191China

Although the functions of metabolic enzymes and nuclear receptors in controlling physiological homeostasis have been established, their crosstalk in modulating metabolic disease has not been explored.Genetic ablation of the xenobiotic-metabolizing cytochrome P450 enzyme CYP2 E1 in mice markedly induced adipose browning and increased energy expenditure to improve obesity. CYP2 E1 deficiency activated the expression of hepatic peroxisome proliferator-activated receptor alpha(PPARa) target genes,including fibroblast growth factor(FGF) 21, that upon release from the liver, enhanced adipose browning and energy expenditure to decrease obesity. Nineteen metabolites were increased in Cyp2 e1-null mice as revealed by global untargeted metabolomics, among which four compounds, lysophosphatidylcholine and three polyunsaturated fatty acids were found to be directly metabolized by CYP2 E1 and to serve as PPARa agonists, thus explaining how CYP2 E1 deficiency causes hepatic PPARa activation through increasing cellular levels of endogenous PPARa agonists. Translationally, a CYP2 E1 inhibitor was found to activate the PPARa-FGF21-beige adipose axis and decrease obesity in wild-type mice, but not in liver-specific Pparanull mice. The present results establish a metabolic crosstalk between PPARa and CYP2 E1 that supports the potential for a novel anti-obesity strategy of activating adipose tissue browning by targeting the CYP2 E1 to modulate endogenous metabolites beyond its canonical role in xenobiotic-metabolism.

关键词： CYP2E1 PPARa FGF21 Metabolic enzyme Nuclear receptor Obesity

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Delivery or previous cesarean？ A comment on ＂Antepartum hemorrhage from previous-cesarean-sectioned uterus as a potential sign of uterine artery pseudoaneurysm＂

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2017年第8期18卷 723-724页

作者： Shigeki MATSUBARA Hironori takahashi Daisuke MATSUBARA Yosuke BABA Department of Obstetrics and Gynecology Jichi Medical University329-0498 Tochigi Japan Department of Pediatrics Jichi Medical University 329-0498Tochigi Japan

Uterine artery pseudoaneurysm （UAP）, an im-portant disorder causing postpartum hemorrhage, hasbeen considered to occur after ＂traumatic delivery＂such as cesarean section （CS）. Our recent study （Babaet al., 2016... 详细信息

关键词：浙江大学学报英文版

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SNOM Observations of Surface Plasmon Polaritons on Metal Heterostructures

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Chinese Physics Letters 2007年第10期24卷 2827-2829页

作者： KITAZAWA Tazuko MIYANISHI Shintaro MURAKAMI Yoshiteru KOJIMA Kunio takahashi Akira Advanced Technology Research Laboratories SHARP CORPORATION 2613-1 Ichinomoto-cho Tenri Nara Japan

我们与一台散布类型的扫描近地的光显微镜(SNOM ) 在一件 metalheterostructured 样品上观察表面电浆子电磁声子(SPP ) 折射。Thesample 由其边界与合适的蚀刻的时间足够光滑的艾尔和 Au 在里面飞机组成。到边界和 SPP 的部分的艾尔电... 详细信息

我们与一台散布类型的扫描近地的光显微镜(SNOM ) 在一件 metalheterostructured 样品上观察表面电浆子电磁声子(SPP ) 折射。Thesample 由其边界与合适的蚀刻的时间足够光滑的艾尔和 Au 在里面飞机组成。到边界和 SPP 的部分的艾尔电影旅行上的 SPPsexcited 宣传进 Au 电影。Inaddition，干扰穗在边界出现在 SNOM 图象偏好。结果与有效索引方法被分析，测定角度被解释由敏捷的法律。

关键词：金属异质结构表面结构分子构成物理分析

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Micro-scale Additive Manufacturing Using the Optical Potential Generated by a Bessel Beam

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Nanomanufacturing and Metrology 2020年第4期3卷 292-298页

作者： Masaki Michihata Makoto Yokei Shotaro Kadoya Satoru takahashi Department of Precision Engineering The University of Tokyo7-3-1 HongoBunkyoTokyo 113-8654Japan Research Center for Advanced Science and Technology The University of Tokyo4-6-1 KomabaMeguroTokyo 153-8904Japan

In this study,we proposed a novel micro-scale additive manufacturing method based on the optical potential formed by a Bessel beam.The proposed technique is expected to show no deterioration in manufacturing resolution due to heat genera-tion,to be applicable to various materials,and to be able to be performed in an air environment.The basic principle of the proposed method involves accumulating and stacking particles dispersed in air by using optical radiation pressure.In this paper,the trajectory of the accumulated particles was numerically estimated and experimentally observed.The numerical and experimental results agreed well;specfially,the back ground flow carried the particles to the optical axis of the Bessel beam,and then the particles were localized at the bottom of the optical potential valley on the substrate.Finally,a pillar structure was fabricated with polystyrene particles having a diameter of 1 um,which indicated that the proposed technique was promising for practical applications.

关键词： Additive manufacturing Optical radiation pressure Optical trapping potential Bessel beam Nanoparticles

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接受抗高血压药治疗的高血压患者夜间高血压的影响因素

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中华高血压杂志(中英文) 2024年第3期32卷 300-300页

作者： Maruhashi T Kinoshita Y Ozono R Nakamaru M Ninomiya M Oiwa J Kawagoe T Yoshida O Matsumoto T Fukunaga Y Sumii K Ueda H Shiode N Takahari K Hayashi Y Ono Y Nakano Y takahashi M Kihara Y Higashi Y 刘青练桂丽

背景：通过家庭血压监测（home blood pressure monitoring,HBPM）设备评估的夜间高血压与心血管事件风险增加相关。然而，经常评估夜间血压仍然很困难。该项横断面研究的目的是确定设备对接受抗高血压药治疗的高血压患者采用HBPM设备...

背景：通过家庭血压监测（home blood pressure monitoring,HBPM）设备评估的夜间高血压与心血管事件风险增加相关。然而，经常评估夜间血压仍然很困难。该项横断面研究的目的是确定设备对接受抗高血压药治疗的高血压患者采用HBPM设备评估的夜间高血压的影响因素。方法：研究者使用HBPM设备连续7d测量365例接受药物治疗的高血压患者的夜间血压、早晨血压、晚上血压和睡前血压。

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TEMPERATURE-DRIVEN SURFACE MORPHOLOGY EVOLUTION OF POLY(3-HYDROXYBUTYRATE) SINGLE LAYER AND POLY(3-HYDROXYBUTYRATE)/POLY(VINYL PHENOL) BILAYER ON Si WAFERS

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Chinese Journal of Polymer Science 2013年第3期31卷 407-418页

作者： Chun-zhu Yan Lin Guo 孙晓丽闫寿科 Isao takahashi School of Chemistry and Environment Beihang University State Key Laboratory of Chemical Resource Engineering Beijing University of Chemical Technology School of Science and Technology Kwansei Gakuin University

The specular and off-specular X-ray reflectivities were efficiently employed to study the evolution of surface morphology as a function of temperature in a single layer of poly（3-hydroxybutyrate）（PHB） and a bilayer of PHB/poly（vinyl phenol）（PVPh） on Si substrates. The results indicate that the changes of thickness and surface roughness caused by pre-melting of PHB crystals are not obvious for the single layer, whereas the surface roughness of the PHB layer and the intensity of the off-specular X-ray reflectivity for the bilayer exhibit a remarkable non-monotonic change in the temperature range of 100-150℃; the roughness parameter evaluated by the specular X-ray reflectivity reaches its maximum at 120℃. The interaction at the interface between PVPh and PHB certainly contributes to the non-monotonic changes. Such interaction also affects the crystallization and melting behavior of PHB thin film greatly. The crystallization of PHB thin film is inhibited even on the glassy surface of PVPh sublayer, In the melting process, the PHB crystals on PVPh sublayer feature a threesection melting curve separated by a plateau region of 120-140℃.

关键词： Interface Hydrogen-bond Roughness Melt.

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Pseudogap,Fermi arc,and Peierls-insulating phase induced by 3D-2D crossover in monolayer VSe2

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Nano Research 2019年第1期12卷 165-169页

作者： Yuki Umemoto Katsuaki Sugawara Yuki Nakata Takashi takahashi Takafumi Sato Department of Physics Tohoku UniversitySendai 980-8578Japan WPI-Advanced Institute for Materials Research Tohoku UniversitySendai 980-8577Japan Center for Spintronics Research Network Tohoku UniversitySendai 980-8577Japan

One of important challenges in condensed-matter physics is to realize new quantum states of matter by manipulating the dimensionality of materials,as represented by the discovery of high-temperature superconductivity in atomic-layer pnictides and room-temperature quantum Hall effect in graphene.Tran sition-metal dichalcogenides(TMDs)provide a fertile platform for exploring novel quantum phenomena accompanied by the dimensionality change,since they exhibit a variety of electronic/magnetic states owing to quantum confinement.Here we report an anomalous metal-i nsulator transition in duced by three-dimensional(3D)-two-dimensional(2D)crossover in mono layer 1T-VSe2 grown on bilayer graphene.We observed a complete insulating state with a finite energy gap on the entire Fermi surface in monolayer 1T-VSe2 at low temperatures,in sharp contrast to metallic nature of bulk.More surprisingly,monolayer 1T-VSe2 exhibits a pseudogap with Fermi arc at temperatures above the charge-density-wave temperature,showing a close resemblanee to high-temperature cuprates.This similarity suggests a common underlying physics between two apparently different systems,pointing to the importance of charge/spin fluctuations to create the novel electronic states,such as pseudogap and Fermi arc,in these materials.

关键词： transition-metal dichalchogenides 1T-VSe2 charge density wave electronic states pseudogap Fermi arc

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Effects of liraglutide on metabolic syndrome in WBN/Kob diabetic fatty rats supplemented with a high-fat diet

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Animal Models and Experimental Medicine 2020年第1期3卷 62-68页

作者： Noriyuki Kaji Yoshiichi Takagi Satomi Matsuda Anna takahashi Sakurako Fujio Fumitoshi Asai Laboratory of Veterinary Pharmacology School of Veterinary MedicineAzabu UniversityKanagawaJapan

Background:Liraglutide,a GLP-1 receptor agonist,has recently been used to treat metabolic syndrome(MS)because of its anti-diabetic and anti-obesity effects.We have previously shown that Wistar Bonn Kobori diabetic and fatty(WBN/Kob-Leprfa,WBKDF)rats fed a high-fat diet(HFD)developed MS including marked obesity,hyperglycemia,and dyslipidemia.To obtain further information on WBKDF-HFD rats as a severe MS model,we performed a pharmacological investigation into the anti-MS effects of liraglutide in this model.Methods:Seven-week-old male WBKDF-HFD rats were allocated to three groups(n=8 in each group):a vehicle group,a low-dose liraglutide group,and a high-dose liraglutide group.They received subcutaneous injections of either saline or liraglutide at doses of 75 or 300μg/kg body weight once daily for 4 weeks.Results:Results showed that liraglutide treatment reduced body weight gain and food intake in a dose-dependent manner.The marked hyperglycemia and the glucose tolerance were also significantly ameliorated in the liraglutide-treated groups.Moreover,liraglutide also reduced the plasma triglyceride concentration and liver fat accumulation.Conclusions:The present study demonstrated that liraglutide could significantly alleviate MS in WBKDF-HFD rats,and the reaction to liraglutide is similar to human patients with MS.WBKDF-HFD rats are therefore considered to be a useful model for research on severe human MS.

关键词： diabetes mellitus liraglutide metabolic syndrome models animal obesity

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Local recurrence after successful endoscopic submucosal dissection for rectal mucinous mucosal adenocarcinoma:A case report

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World Journal of Gastrointestinal Oncology 2023年第1期15卷 186-194页

作者： Yuki Murakami Hiroki Tanabe Yusuke Ono Yuya Sugiyama Yu Kobayashi Takehito Kunogi Takahiro Sasaki Keitaro takahashi Katsuyoshi Ando Nobuhiro Ueno Shin Kashima Sayaka Yuzawa Kentaro Moriichi Yusuke Mizukami Mikihiro Fujiya Toshikatsu Okumura Division of Metabolism and Biosystemic Science Department of Gastroenterology and Hematology/OncologyDepartment of MedicineAsahikawa Medical UniversityAsahikawa 078-8510HokkaidoJapan Institute of Biomedical Research Sapporo-Higashi Tokushukai HospitaSapporo 065-0033HokkaidoJapan Department of Diagnostic Pathology Asahikawa Medical UniversityAsahikawa 078-8510HokkaidoJapan

BACKGROUND Mucinous adenocarcinoma of the colorectum is a rare histological subtype characterized by an abundant mucinous component.Mucinous tumors are frequently diagnosed at an advanced stage,which indicates an aggressive subtype.However,few case reports have been published,and little information is available concerning genetic alterations in mucinous adenocarcinoma.CASE SUMMARY A 76-year-old man underwent en bloc endoscopic submucosal dissection(ESD)for the management of a type 0-Is+IIa lesion.Histological examination revealed an intramucosal mucinous adenocarcinoma with signet-ring cell carcinoma and well-to-moderately differentiated tubular adenocarcinoma.Three years after the ESD,local recurrence was detected by an endoscopic examination,revealing a new 0-Is+IIa lesion with a phenotype similar to the previously resected lesion.Re-ESD was chosen for the management of the recurrent tumor,and the histological examination showed positive tumor infiltration at the vertical margin.Additional surgical resection was performed for the curative treatment.Genetic analysis showed pathogenic alterations in RNF43 and TP53 in the adenoma and an additional SMAD4 alteration in the carcinoma.CONCLUSION This mucinous mucosal adenocarcinoma case was suggested to have an aggressive phenotype and a careful and close follow-up are required.

关键词： Rectal cancer Mucinous adenocarcinoma Endoscopic submucosal dissectio TP53 Colitic cancer pathway Case report

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Application of Scanning Acoustic Microscopy for Detection of Dental Caries Lesion

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Open Journal of Stomatology 2023年第1期13卷 12-24页

作者： Yukihiro Naganuma Kouki Hatori Masahiro Iikubo Masatoshi takahashi Yoshihiro Hagiwara Kazuto Kobayashi Atsushi takahashi Kumi Hoshi Yoshifumi Saijo Keiichi Sasaki Clinics of Dentistry for Disabled Tohoku University Hospital Sendai Japan Department of Prosthetic Dentistry Ohu University School of Dentistry Koriyama Japan Division of Dental Informatics and Radiology Tohoku University Graduate School of Dentistry Sendai Japan Division of Dental Biomaterials Tohoku University Graduate School of Dentistry Sendai Japan Department of Orthopaedic Surgery Tohoku University School of Medicine Sendai Japan Honda Electronics Co. Ltd. Toyohashi Japan Biomedical Imaging Laboratory Graduate School of Biomedical Engineering Tohoku University Sendai Japan Division of Advanced Prosthetic Dentistry Tohoku University Graduate School of Dentistry Sendai Japan

Introduction: A scanning acoustic microscope (SAM) is an apparatus for imaging acoustic properties. This apparatus can non-invasively and rapidly evaluate the hardness of materials in the elastic region. This device shows great potential for the diagnosis of dental caries in the clinical setting. However, since the tissue elastic modulus measured using a SAM is a property of the elastic region and the Knoop hardness is a property of the plastic region, the hardness properties differ completely. Therefore, we investigated whether the acoustic impedance measured using a SAM is related to the Knoop hardness, which is used as the standard for removal of carious dentin. Method: Polished sections were prepared from 20 extracted carious wisdom teeth. The acoustic impedance and Knoop hardness were measured for each section. In addition to comparing carious and healthy dentin in SAM images, we evaluated the difference between the carious and healthy dentin in terms of the acoustic impedance and Knoop hardness. We also evaluated the correlation between the Knoop hardness and acoustic impedance. Results: The SAM images were visualized as two-dimensional color images based on the acoustic impedance values. The mean acoustic impedance of carious dentin was significantly lower than that of healthy dentin, showing a similar trend as Knoop hardness. A strong correlation was observed between the two. Discussion: The acoustic impedance values obtained through acoustic microscopy differed significantly between carious and sound dentin. Both types of dentins were visualized using two-dimensional color images. A strong correlation was observed between the acoustic impedance value, which indicates the hardness of the elastic region, and the Knoop hardness, which indicates the hardness of the plastic region. The results of the present study indicate that acoustic impedance accurately reflects the hardness of dentin.

关键词： Scanning Acoustic Microscope Acoustic Impedance Caries Knoop Hardness

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