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Phf15-a novel transcriptional repressor regulating inflammation in a mouse microglial cell line

Neuroimmunology and Neuroinflammation 2020年第2期7卷 166-182页

作者： Sandra E.Muroy Greg A.Timblin Marcela K.Preininger Paulina Cedillo Kaoru saijo Department of Molecular and Cell Biology University of CaliforniaBerkeleyCA 94720USA Helen Wills Neuroscience Institute University of CaliforniaBerkeleyCA 94720USA

Aim: Excessive microglial inflammation has emerged as a key player in mediating the effects of aging and neurodegeneration on brain dysfunction. Thus, there is great interest in discovering transcriptional repressors that can control this process. We aimed to examine whether Phf15 - one of the top differentially expressed genes in microglia during aging in humans - could regulate transcription of proinflammatory mediators in microglia. Methods: Real-time quantitative PCR was used to assess Phf15 mRNA expression in mouse brain during aging. Loss-of-function [short hairpin RNA (shRNA) -mediated knockdown (KD) and CRISPR/Cas9-mediated knockout (KO) of Phf15] and gain-of-function [retroviral overexpression (OE) of murine Phf15 cDNA] studies in a murine microglial cell line (SIM-A9) followed by immune activation with lipopolysaccharide were used to determine the effect of Phf15 on proinflammatory factor (Tnfα , IL-1β , and Nos2) mRNA expression. RNA sequencing was used to determine global transcriptional changes afterPhf15 knockout under basal conditions and after lipopolysaccharide stimulation. Results:Phf15 expression increases in mouse brain during aging, similar to humans. KD, KO, and OE studies determined that Phf15 represses mRNA expression levels of proinflammatory mediators such as Tnfα , IL-1β , and Nos2 . Global transcriptional changes after Phf15 KO showed that Phf15 specifically represses genes related to the antiviral (type I interferon) response and cytokine production in microglia. Conclusion: We provide the first evidence thatPhf15 is an important transcriptional repressor of microglial inflammation, regulating the antiviral response and proinflammatory cytokine production. Importantly, Phf15 regulates both basal and signal-dependent activation and controls the magnitude and duration of the microglial inflammatory response.

关键词： Phf15 microglia transcriptional repression neuroinflammation

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Distant metastasis of hepatocellular carcinoma to Meckel’s cave and cranial nerves:A case report and review of literature

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World Journal of Hepatology 2021年第6期13卷 709-716页

作者： Soo Ki Kim Takako Fujii Ryouhei Komaki Hisato Kobayashi Toyokazu Okuda Yumi Fujii Takanobu Hayakumo Kanako Yuasa Masahiro Takami Aya Ohtani Yuka saijo Yu-Ichiro Koma Soo Ryang Kim Department of Gastroenterology Kobe Asahi HospitalKobe 653-0801HyogoJapan Division of Neurology Kobe University Graduate School of MedicineKobe 650-0017HyogoJapan Department of Radiology Kobe Asahi HospitalKobe 653-0801HyogoJapan Department of Pharmacy Kobe Asahi HospitalKobe 653-0801HyogoJapan Department of Pathology Kobe University Graduate School of MedicineKobe 650-0017HyogoJapan

BACKGROUND Metastasis occurs as a late event in the natural history of hepatocellular carcinoma(HCC),and most patients die of liver failure attributed to the tumor supplanting the ***,the brain is a less common metastatic *** SUMMARY We describe a rare case of hepatitis C virus-related multiple HCC metastasizing to the cavernous sinus,Meckel’s cave,and the petrous bone involving multiple cranial nerves in an 82-year-old *** admission imaging studies including Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(MRI)revealed multiple HCC nodules in both right and left *** guided biopsy of the left lobe revealed moderately differentiated *** targeted therapy with Lenvatinib(8 mg/d for 94 d,per os)and Ramucirumab(340 mg/d and 320 mg/d,two times by intravenous injection)were administered for 4 mo,resulting in progression of the *** months after the start of molecular target therapy,the patient presented with symptoms of hyperalgesia of the right face and limited abduction of the right eye,indicating disturbances in the right trigeminal and abducens *** MRI disclosed a mass involving the cavernous sinus,Meckel’s cave and the petrous ***-enhanced MRI with gadolinium-chelated contrast medium revealed a well-defined mass with abnormal enhancement around the right cavernous sinus and the right Meckel’s *** The diagnosis of metastatic HCC to the cavernous sinus,Meckel’s cave,and the petrous bone was made based on neurological findings and imaging studies including MRI,but not on histological *** studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

关键词： Meckel’s cave Abducens nerve Trigeminal nerve Hepatocellular carcinoma Magnetic resonance imaging Case report

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A new diagnostic feasibility for cardiomyopathy utilizing acoustic microscopy

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World Journal of Cardiovascular Diseases 2013年第1期3卷 22-30页

作者： Yoichi Nakamura Kengo Fukushima Kusano Kazufumi Nakamura Kazuto Kobayashi Naohiro Hozumi Yoshifumi saijo Tohru Ohe Biomedical Imaging Laboratory Graduate School of Biomedical Engineering Tohoku University Sendai Japan Department of Cardiology Sakakibara Heart Institute of Okayama Okayama Japan Department of Cardiovascular Medicine Matsuyama Shimin Hospital Matsuyama Japan Department of Research and Development Honda Electronics Co. Ltd. Toyohashi Japan epartment of Cardiovascular Medicine Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan Toyohashi University of Technology International Cooperation Center for Engineering Education Development Toyohashi Japan

Aims: Dilated cardiomyopathy often shows left ventricular systolic dysfunction, although histologically it always exhibits non-specific abnormality. We hypothesized that myocyte sound speed might be altered due to incomplete protein accumulation in cells. Methods and Results: Ninety eight biopsied samples were obtained from 49 patients comprising 43 with clinical dilated cardiomyopathy and 6 with hypertrophic cardiomyopathy. Sound speed was evaluated in deparaffinized 10 μm thick sections using an acoustic microscope (frequency range: 50 - 105 MHz). Conventional histology revealed 7 cases of persistent myocarditis derived from clinical dilated cardio- myopathy samples. Histology of the remaining dilated cardiomyopathy patients indicated non-specific abnormality. All hypertrophic cardiomyopathy cases exhibited myocardial disarray. Ten normal autopsied hearts were compared as controls. The sound speed of controls was 1627 ± 30m/sec. The sound speed in dilated cardiomyopathy samples (1700 ±51m/sec) was 1.045-fold faster compared to controls. The sound speed in hypertrophic cardiomyopathy samples (1734 ±51m/sec, 1.066-fold compared to controls) was faster than that of the myocarditis group (1672 ±30m/sec, 1.028-fold) (P = 0.0218). Furtheremore, desmin expression was evaluated as extent of emergence (grading 0 - 4). The desmin expression score in hypertrophic cardiomyopathy samples (2.7 ± 0.8) was significantly higher than in other groups (dilated 2.0 ± 1.4, myocarditis 1.6 ± 1.5 vs., controls 0, P ≤ 0.0001, 0.0001, 0.0129, respectively). Conclusion: Cardio-myopathy enhanced the sound speed, which correlated with the elasticity of myocytes, following the impaired compliance of left ventricle, despite the absence of histological changes. The elevation of sound speed of myocytes may be linked to cytoskeletal changes. Myocyte sound speed may be a new diagnostic tool for diagnosis of idiopathic cardiomyopathy independently of conventional histological diagnosis.

关键词： Cardiomyopathy Acoustic Microscopy Heart Failure Myocytes Sound Speed Diagnosis

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传染性法氏囊病病毒减毒蚀斑变异株的分离和鉴定

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国外兽医学（畜禽传染病） 1991年第1期11卷 15-17页

作者： saijo,K 晁毓放

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A Case of Pleomorphic Adenoma of the Parotid Gland with Multiple Local Recurrences through Facial to Cervical Regions

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Open Journal of Stomatology 2014年第9期4卷 441-445页

作者： Masanobu Abe Yoshiyuki Mori Yuki Kanno Kazuto Hoshi Hideto saijo Takahiro Abe Kazumi Ohkubo Tsuyoshi Takato Department of Oral & Maxillofacial Surgery University of Tokyo Hospital Tokyo Japan

Pleomorphic adenoma is the most common benign parotid gland tumor. Although its local recurrence rate is known to be high, the recurrence extending to the cervical region is rare. Here we report a case of a young female (25 years old) with pleomorphic adenoma of the parotid gland which showed multiple recurrences through facial to cervical regions over a span of eight years. We also discuss how this benign tumor with a high recurrence rate has been treated in other cases, and how it should be treated.

关键词： Pleomorphic Adenoma Parotid Gland Salivary Neoplasm

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Hollow Fiber Module Applied for Effective Proliferation and Harvest of Cultured Chondrocytes

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Materials Sciences and Applications 2013年第8期4卷 62-67页

作者： Yoshiyuki Mori Makoto Watanabe Sakae Nakagawa Yukiyo Asawa Satoru Nishizawa Kazumi Okubo Hideto saijo Satoru Nagata Yuko Fujihara Tsuyoshi Takato Kazuto Hoshi Department of Cartilage & Bone Regeneration (Fujisoft) Graduate School of Medicine The University of Tokyo Tokyo Japan Department of Cartilage & Bone Regeneration (Fujisoft) Graduate School of Medicine The University of Tokyo Tokyo Japan Division of Tissue Engineering The University of Tokyo Hospital Tokyo Japan Department of Sensory and Motor System Medicine Graduate School of Medicine The University of Tokyo Tokyo Japan Department of Sensory and Motor System Medicine Graduate School of Medicine The University of Tokyo Tokyo Japan Department of Cartilage & Bone Regeneration (Fujisoft) Graduate School of Medicine The University of Tokyo Tokyo Japan Division of Tissue Engineering The University of Tokyo Hospital Tokyo Japan Department of Sensory and Motor System Medicine Graduate School of Medicine The University of Tokyo Tokyo Japan Division of Tissue Engineering The University of Tokyo Hospital Tokyo Japan NAGATA Microtia and Reconstructive Plastic Surgery Clinic Saitama Japan Nomura Unison Co. Ltd Nagano Japan

Steady and useful culture for chondrocytes is essential for cartilage regenerative medicine. However, in conventional plate culture, the chondrocytes become dedifferentiated and lose their ability to make cartilage matrices. Three-dimensional culture mimicking the physiological environment in native chondrocytes is useful to maintain the chondrocyte properties during the proliferation culture. However, the three-dimensional culture is practically a hard task due to difficult harvest of the cells. Thus, we attempted to apply porous materials, hollow fibers for the three-dimensional culture, and developed their module to realize the effective harvest of the cells. Polyethersulfone-based hollow fibers, whose safety and cell affinity were confirmed by the experiment of the coculture with human chondrocytes, were collected to fabricate a module. The hollow fiber module was installed with screw ends, and enabled the easy removal of chondrocytes from the inner unit. Cultured human chondrocytes embedded within collagen hydrogel were put into the outer lumen of the hollow fiber module, while chondrocyte prolfieration medium was perfused through the inner lumen at 0 to 30 mL/min. After 2 weeks’ culture, the flow rate of 3 to 10 mL/min effectively supported the chondrocyte proliferation. Then, long-term culture using the hollow fiber module at flow rate of 5 mL/min was performed, revealing that the cell growth in this module at 3 weeks was approximately twice larger than that in static culture. The numbers of viable cells could be maintained by week 7. The hollow fiber module installed with screw ends can effectively culture and harvest the chondrocytes.

关键词： Hollow Fiber Module Proliferation Cell Culture Chondrocyte Tissue Engineering

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新疆出血热病毒分子流行病学研究

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中华实验和临床病毒学杂志 2005年第4期19卷 312-318页

作者：唐青赵秀芹王环宇司马义巴吾东张玉贞 Masayuki saijo Shigeru Morikawa 梁国栋 Ichiro Kurane 中国疾病预防控制中心病毒病预防控制所病毒性脑炎室北京100052 中国疾病预防控制中心传染病预防控制所结核室新疆巴楚县疾病预防控制中心新疆巴楚县人民医院日本国立感染症研究所病毒I室

目的研究新疆出血热病毒(XHF)分子流行病学,揭示其与相关病毒之间关系,分析XHF的流行来源和分布特点。方法RTPCR检测20012002年XHF患者和蜱标本中XHF病毒S基因,阳性标本直接进行核苷酸序列测定。计算机软件进行S基因部分片段和S全基因... 详细信息

目的研究新疆出血热病毒(XHF)分子流行病学,揭示其与相关病毒之间关系,分析XHF的流行来源和分布特点。方法RTPCR检测20012002年XHF患者和蜱标本中XHF病毒S基因,阳性标本直接进行核苷酸序列测定。计算机软件进行S基因部分片段和S全基因序列同源性比较和S基因、M基因的种系发生树分析。结果不同年份人和蜱来源的病毒S基因部分片段核苷酸序列均显示较高同源性(97.3%～100%)。S基因进化树分析将病毒分成了欧洲、非洲和亚洲3组,其中亚洲毒株由中亚分离株和中国分离株组成,中国所有的XHF病毒S基因(同源性93.0%～99.5%)均集中在一个分枝下形成独立的一组,明显区别于世界上其他地区分离株(同源性81.40%～96.4%)。M基因进化树分析表明序列间差异不完全与病毒分离的地理区域相关。结论S基因分析显示XHF病毒蜱分离株与人分离株遗传背景接近,我国XHF病毒有共同的进化途径和基因结构特点,并具明显的地域性。

关键词：出血热,克里米亚流行病学,分子序列分析

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用扫描声学显微镜对梗塞心肌进行超声组织定征

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上海生物医学工程 1997年第3期18卷 44-47页

作者： saijo Y Tanaka M Okawai H 王志刚

本研究的目的,是用扫描声学显微镜在显微水平,对人的梗塞心肌进行超声组织定征。对10例心肌梗塞患者的心肌标本进行研究,标本用福尔马林固定,石腊包埋,并切片到10μm的厚度。使用一套特别设计的、100～200MHz超声频率的声学显微镜进行... 详细信息

本研究的目的,是用扫描声学显微镜在显微水平,对人的梗塞心肌进行超声组织定征。对10例心肌梗塞患者的心肌标本进行研究,标本用福尔马林固定,石腊包埋,并切片到10μm的厚度。使用一套特别设计的、100～200MHz超声频率的声学显微镜进行测量。正常心肌衰减的系数值是0.94±0.04dB/mm/MHz,变性心肌是0.71±0.12dB/mm/MHz,肉芽组织是0.88±0.47dB/mm/MHz,纤维化组织是1.75±0.11dB/mm/MHz。正常组织的声速是1620.2±8.2m/s,变性心肌是1572.4±10.6m/s,肉芽组织是1590.2±32.5m/s,纤维化组织是1690.3±9.1m/s。病变心肌在显微水平的超声性质,将提供大体水平的重要的超声组织定征资料。

关键词：心肌梗塞超声组织定征声学显微镜

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Dectin-2 selectively suppresses liver metastasis by facilitating the uptake of cancer cells by Kupffer cells

Dectin-2 selectively suppresses liver metastasis by facilita...

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第十一届全国免疫学学术大会

作者： Yoshitaka Kimura Hideyuki Yanai Sho Hangai Asuka Inoue Junko Nishio Hideo Negishi Shinobu saijo Yoichiro Iwakura Sho Yamasaki Tadatsugu Taniguchi Institute of Industrial Science The University of Tokyo Max Planck-The University of Tokyo Center for Integrative Inflammology Department of Molecular Immunology Medical Mycology Research Center Chiba University Center for Animal Disease Models Research Institute for Biomedical Sciences Tokyo University of Science Division of Molecular Immunology Medical Institute of Bioregulation Kyushu University

Metastasis to distal organ is a fatal cause of cancer death and liver is one of the most common site of metastasis leading to bad *** it has been known that innate immune cells play critical roles in the regulation of liver metastasis,how they control the tumor development is still largely *** using in vivo cancer models,we found that Dectin-2,a C-type lectin receptor(CLR),suppressed liver metastasis although dispensable for the

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Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses

Recognition of tumor cells by Dectin-1 orchestrates innate i...

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第九届全国免疫学学术大会

作者： Yoshitaka Kimura Shiho Chiba Hiroaki Ikushima Hiroshi Ueki Hideyuki Yanai Sho Hangai Junko Nishio Hideo Negishi Tomohiko Tamura Shinobu saijo Yoichiro Iwakura Tadatsugu Taniguchi Department of Molecular Immunology and Center for International Research on Integrative Biomedical Systems Institute of Industrial ScienceThe University of Tokyo Max Planck-The University of Tokyo Center for Integrative Inflammology Core Research for Evolution Science and Technology Japan Science and Technology Agency Department of Immunology Yokohama City University Graduate School of Medicine Department of Molecular Immunology Medical Mycology Research CenterChiba University Center for Animal Disease Models Research Institute for Biomedical SciencesTokyo University of Science

Innate immune receptors play pivotal roles in the immune response against invading ***,the role of such receptors in anti-tumor immune responses is still *** gain insights into the role of innate immune

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