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Pharmacology & Pharmacy 2016年第7期7卷 272-282页

作者： yoshiyuki hattori Department of Drug Delivery Research Hoshi University Tokyo Japan

For systemic injection of cationic liposome/plasmid DNA (pDNA) complexes (cationic lipoplexes), polyethylene glycol (PEG)-modification (PEGylation) of lipoplexes can enhance their systemic stability. In this study, we examined whether intravenous injection of PEGylated cationic lipoplexes into tumor-bearing mice could deliver pDNA into tumor tissues and induce transgene expression. PEGylation of cationic liposomes could prevent their agglutination with erythrocytes. However, when PEGylated cationic lipoplexes were injected intravenously into tumor-bearing mice, they accumulated in tumor vascular vessels and did not exhibit transgene expression in tumors with both poor and well-developed vascularization. Furthermore, PEGylated cationic lipoplexes of CpG- free pDNA could not increase transgene expression in tumors after intravenous injection. These results suggested that PEGylation could not extravasate cationic lipoplexes from vascular vessels in tumors and abolished transgene expression although it enhanced the systemic stability of cationic lipoplexes by avoiding interactions with blood components such as erythrocytes. Successful delivery of pDNA to tumors by PEGylated cationic liposomes will require a rational strategy and the design of liposomal delivery systems to overcome the issue associated with the use of PEG.

关键词： Cationic Liposome Lipoplex Plasmid DNA PEGylation Tumor

Evaluation of Cisplatin-Loaded Polymeric Micelles and Hybrid Nanoparticles Containing Poly(Ethylene Oxide)-Block-Poly(Methacrylic Acid) on Tumor Delivery

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Pharmacology & Pharmacy 2016年第1期7卷 1-8页

作者： Andang Miatmoko Kumi Kawano Etsuo Yonemochi yoshiyuki hattori Department of Drug Delivery Research Hoshi University Shinagawa Japan Department of Physical Chemistry Hoshi University Shinagawa Japan

Particulate carriers such as polymeric micelles (PMs) and liposomes have been investigated to increase drug accumulation in tumors and reduce distribution to healthy tissues. In this study, we prepared PM and hybrid nanoparticles (HNPs) with poly(ethylene oxide)-block-poly(methacrylic acid) (PEO-b-PMAA) for loading cisplatin, and evaluated cisplatin release, cytotoxicity, and biodistribution in mice. PM composed of PEO-b-PMAA and HNPs composed of egg phosphatidylcholine (EPC)/PEO-b-PMAA at molar ratios of 50/2.8 (HNP-P5) and 50/50 (HNP-P50), respectively, were prepared by a nanoprecipitation method. The sizes of PM, HNP-P5, and HNP-P50 after inclusion of cisplatin were approximately 200, 100, and 55 nm, respectively, and their entrapment efficiencies were approximately 44% - 66%. In the drug-release study, HNP-P5 and HNP-P50 showed reduced release of cisplatin compared with PM. Regarding the cytotoxic assay, HNP-P5 exhibited lower cytotoxicity for mouse Lewis lung carcinoma (LLC) and mouse colon carcinoma Colon 26 cells than PM and HNP-P50. In terms of biodistribution, PM could significantly improve blood circulation and tumor accumulation after intravenous injection into Colon 26 tumor-bearing mice compared with free cisplatin, but HNP-P5 and HNP-P50 did not. EPC in HNPs might be destabilized in the circulation, although it could reduce release of cisplatin in in vitro experiments. This study suggested that polymeric micelles composed of PEO-b-PMAA are a better carrier for cisplatin than hybrid nanoparticles composed of PEO-b-PMAA and EPC.

关键词： Polymeric Micelles Hybrid Nanoparticles Cisplatin PEO-b-PMAA

Evaluation of Small Interfering RNA Delivery into Cells by Reverse Transfection in Suspension with Cationic Liposomes

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Pharmacology & Pharmacy 2017年第5期8卷 129-139页

作者： yoshiyuki hattori Yuki Yoshiike Maho Honda Hiroaki Ohno Hiraku Onishi Department of Drug Delivery Research Hoshi University Shinagawa Japan Graduate School of Pharmaceutical Sciences Kyoto University Kyoto Japan

Successful gene silencing by small interfering RNA (siRNA) requires efficient uptake of siRNA into targeted cells. For in vitro transfection of siRNA using cationic liposomes, two types of transfection method are currently being used: conventional (forward;Fw) and reverse (Rev) transfections. Here, to investigate an efficient siRNA transfection method using cationic liposomes, we compared the transfection efficiency of siRNA between Fw-transfection and Rev-transfection methods with various types of cationic liposomes. In Fw-transfection, siRNA/cationic liposomes complex (siRNA lipoplexes) was added to pre-plated cells. In contrast, Rev-transfection was performed by co-incubation of cells with siRNA lipoplexes in suspension. As a result, Rev-transfection with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)-based or cationic cholesterol derivative-based liposomes could deliver siRNA into the cells via efficient cellular association, and induce an improved gene silencing effect by siRNA compared with Fw-transfection. Furthermore, Rev-transfection did not show increased cytotoxicity compared with Fw-transfection. These findings suggested that Rev-transfection in suspension has better potential for efficient transfection of siRNA into cells with minimal toxicity.

关键词： Cationic Liposome siRNA Delivery Reverse Transfection Tumor Cells

Influence of aging,mitochondrial dysfunction,and inflammation on Parkinson's disease

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Neural Regeneration Research 2024年第6期19卷 1197-1198页

作者： Davide Cossu Nobutaka hattori Department of Neurology Juntendo UniversityTokyoJapan Department of Biomedical Sciences Sassari UniversitySassariItaly

Aging is associated with chronic form of inflammation called inflammaging,which results from immune system *** plays a crucial role in the pathogenesis of various neurodegenerative diseases(Dabravolski et al.,2022).Mo... 详细信息

关键词： inflammation aging

Optimization of siRNA Delivery Method into the Liver by Sequential Injection of Polyglutamic Acid and Cationic Lipoplex

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Pharmacology & Pharmacy 2015年第7期6卷 302-310页

作者： yoshiyuki hattori Shohei Arai Takuto Kikuchi Megumi Hamada Ryou Okamoto Yoko Machida Kumi Kawano Department of Drug Delivery Research Hoshi University Tokyo Japan

Previously, we developed a novel siRNA transfer method to the liver by sequential intravenous injection of poly-L-glutamic acid (PGA) and cationic liposome/siRNA complex (cationic lipoplex). In this study, we examined the effects of the charge ratio (+/-) of cationic liposome/siRNA, molecular weight of PGA and cationic lipid of cationic liposome on the biodistribution of siRNA after sequential injection of PGA plus cationic lipoplex. When 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol (Chol) lipoplex was intravenously injected into mice, the accumulation of siRNA was mainly observed in the lungs. In contrast, when DOTAP/Chol lipoplex was intravenously injected at 1 min after intravenous injection of PGA, siRNA was largely accumulated in the liver. The charge ratio (+/-) of DOTAP/Chol liposome/siRNA did not affect the biodistribution of siRNA after sequential injection. As regards the molecular weight of PGA, the accumulation of siRNA was observed mainly in the liver after the sequential injection of PGA of 20.5, 38, 64 or 200 kDa plus DOTAP/Chol lipoplex. Furthermore, to examine the effect of cationic lipid of cationic liposome on the biodistribution of siRNA, we prepared other cationic liposomes composed of 1,2-di-O-octadecenyl-3-trimethylammonium propane chloride (DOTMA)/Chol, dimethyldioctade-cylammonium bromide (DDAB)/Chol and O,O’-ditetradecanoyl-N-(α-trimethylammonioacetyl)di-ethanolamine chloride (DC-6-14)/Chol. For the cationic liposomes, the accumulation of siRNA was observed mainly in the liver when their cationic lipoplexes were sequentially injected after injection of PGA into mice. From these findings, sequential injection of PGA plus cationic lipoplex could deliver siRNA efficiently into the liver regardless of the charge ratio (+/-) of lipoplex, lengths of PGA and cationic lipid of liposome.

关键词： Cationic Liposome siRNA Delivery Polyglutamic Acid Liver Targeting Sequential Injection

Aging-induced memory loss due to decreased N1-acetyl-5-methoxykynuramine,a melatonin metabolite,in the hippocampus:a potential prophylactic agent for dementia

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Neural Regeneration Research 2025年第6期20卷 1705-1706页

作者： Kazuki Watanabe Atsuhiko hattori Department of Immunobiology Institute of Development Aging and CancerTohoku UniversitySendaiMiyagiJapan Department of Sport and Wellness College of Sport and WellnessRikkyo UniversityNiizaSaitamaJapan

Melatonin(N-acetyl-5-methoxytryptamine)is known as the hormone of darkness because it is synthesized at night and involved in regulating the circadian *** hormone is primarily synthesized by the vertebrate pineal gland,but is ubiquitous among invertebrates,unicellular organisms,plants,and even cyanobacteria(hattori and Suzuki,2024).Melatonin is well-conserved evolutionarily and possesses several physiological functions,such as immune response,bone and glucose metabolism,and memory formation besides regulating the circadian rhythm.

关键词： metabolism primarily agent

Strong coupling and catenary field enhancement in the hybrid plasmonic metamaterial cavity and TMDC monolayers

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Opto-Electronic Advances 2024年第5期7卷 20-32页

作者： Andergachew Mekonnen Berhe Khalil As’ham Ibrahim Al-Ani Haroldo T.hattori Andrey E.Miroshnichenko School of Engineering and Technology University of New South Wales at CanberraNorthcott DriveCanberra ACT 2610Australia

Strong coupling between resonantly matched surface plasmons of metals and excitons of quantum emitters results in the formation of new plasmon-exciton hybridized energy *** plasmon-exciton strong coupling,plasmonic nanocavities play a significant role due to their ability to confine light in an ultrasmall ***,two-dimensional transition metal dichalcogenides(TMDCs) have a significant exciton binding energy and remain stable at ambient conditions,making them an excellent alternative for investigating light-matter *** a result,strong plasmon-exciton coupling has been reported by introducing a single metallic ***,single nanoparticles have lower spatial confinement of electromagnetic fields and limited tunability to match the excitonic ***,we introduce the concept of catenary-shaped optical fields induced by plasmonic metamaterial cavities to scale the strength of plasmon-exciton *** demonstrated plasmon modes of metallic metamaterial cavities offer high confinement and tunability and can match with the excitons of TMDCs to exhibit a strong coupling regime by tuning either the size of the cavity gap or *** calculated Rabi splitting of Au-MoSe_2 and Au-WSe_2 heterostructures strongly depends on the catenary-like field enhancement induced by the Au cavity,resulting in room-temperature Rabi splitting ranging between 77.86 and 320 me *** plasmonic metamaterial cavities can pave the way for manipulating excitons in TMDCs and operating active nanophotonic devices at ambient temperature.

关键词： catenary-shaped field enhancement strong coupling plasmon exciton Rabi splitting

Optimal interval for delayed retrieval surgery with reciprocating morcellators after enucleation of giant prostatic hyperplasia in holmium laser enucleation of the prostate

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Asian Journal of Urology 2024年第3期11卷 423-428页

作者： Fumiyasu Endo Masaki Shimbo Kenji Komatsu Kazuhiro Ohwaki Kazunori hattori Department of Urology St.Luke’s International Hospital9-1 Akashi-choChuo-kuTokyoJapan Department of Hygiene and Public Health Teikyo University School of Medicine Graduate School of Medicine2-11-1 KagaItabashi-kuTokyoJapan

Objective:The aim of this research was to evaluate the efficiency of reciprocating morcellation for removing giant benign prostatic hyperplasia during holmium laser enucleation of the prostate,investigate whether performing morcellation as a two-stage procedure improves tissue retrieval efficiency,and seek to determine the optimal interval between the two ***:This study included nine cases of holmium laser enucleation of the prostate with an enucleated prostate weight exceeding 200 g,indicative of substantial prostate *** was performed on Day 0(n=4),Day 4(n=1),Day 6(n=1),and Day 7(n=3).The intervals were compared regarding the morcellation efficiency,beach ball presence,and ***:The mean estimated prostate volume was 383(range 330e528)mL;the median enucleation weight was 252(interquartile range[IQR]222,342)g;and the median enucleation time was 83(IQR 62,100)*** mean morcellation efficiency was 1.44(SD 0.55)g/min on Day 0 and 13.69(SD 2.46)g/min on day *** morcellation efficiency was 4.15 g/min and 10.50 g/min on Day 4 and Day 6,respectively,with significantly higher in the two-stage group compared to one-stage group(11.0 g/min vs.1.5 g/min;p=0.014).Efficiency was strongly correlated with intervals(p<0.001);the incidences of beach balls were 100%(4/4)and 60%(3/5)in the immediate and two-stage surgery groups,***:The efficiency of two-stage morcellation with reciprocating morcellators was highly related to the postoperative interval,with the maximum efficiency reached on Day 7.

关键词： Holmiumlaser enucleationofthe prostate Reciprocating morcellator Giant adenoma Two-stage surgery

Development of Self-Rated Nursing Record Frequency for Delirium Care of Nurses in Acute Care Hospitals (NRDC-Acute)

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Open Journal of Nursing 2024年第8期14卷 412-420页

作者： Katsuhiko hattori Kenichi Matsuda Department of Nursing Teikyo Heisei University Tokyo Japan

Background: Nursing records play an important role in multidisciplinary collaborations in delirium care. This study aims to develop a self-rated nursing record frequency scale for delirium care among nurses in acute care hospitals (NRDC-Acute). Methods: A draft of the scale was developed after a literature review and meeting with researchers with experience in delirium care, and a master’s or doctoral degree in nursing. We identified 25 items on a 5-point Likert scale. Subsequently, an anonymous self-administered questionnaire survey was administered to 520 nurses from 41 acute care hospitals in Japan, and the reliability and validity of the scale were examined. Results: There were 232 (44.6%) respondents and 218 (41.9%) valid responses. The mean duration of clinical experience was 15.2 years (SD = 8.8). Exploratory factor analysis extracted 4 factors and 13 items for this scale. The model fit indices were GFI = 0.991, AGFI = 0.986, and SRMR = 0.046. The Cronbach’s alpha coefficient for the entire scale was .888. The four factors were named “Record of Pharmacological Delirium Care on Pro Re Nata (PRN)”, “Record of Non-Pharmacological Delirium Care”, “Record of Pharmacological Delirium Care on Regular Medication”, and “Record of Collaboration for Delirium Care”. Conclusion: The scale was relatively reliable and valid. Nurses in acute care hospitals can use this scale to identify and address issues related to the documentation of nursing records for delirium care.

关键词： Acute Care Hospitals Delirium Care Nurses Nursing Records Scale Development

Himalayas as a global hot spot of springtime stratospheric intrusions:Insight from isotopic signatures in sulfate aerosols

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Research in Cold and Arid Regions 2024年第1期16卷 5-13页

作者： Kun Wang ShiChang Kang Mang Lin PengFei Chen ChaoLiu Li XiuFeng Yin Shohei hattori Teresa L.Jackson JunHua Yang YiXi Liu Naohiro Yoshida Mark HThiemens State Key Laboratory of Cryospheric Science Northwest Institute of Eco-Environment and ResourcesChinese Academy of Sciences(CAS)LanzhouGansu 730000China State Key Laboratory of Isotope Geochemistry Guangzhou Institute of GeochemistryCASGuangzhouGuangdong 510640China University of Chinese Academy of Sciences Beijing 100049China International Center for Isotope Effects Research(ICIER) School of Earth Sciences and EngineeringNanjing UniversityNanjingJiangsu 210023China Frontiers Science Center for Critical Earth Material Cycling State Key Laboratory for Mineral Deposits ResearchSchool of Earth Sciences and EngineeringNanjing UniversityNanjingJiangsu 210023China Department of Chemical Science and Engineering School of Materials and Chemical TechnologyTokyo Institute of Technology4259 Nagatsuta-choMidori-kuYokohamaKanagawa 226-8502Japan Department of Chemistry and Biochemistry University of California San DiegoLa JollaCA 92093-0021USA Earth-Life Science Institute Tokyo Institute of TechnologyMeguro-kuTokyo 152-8551Japan National Institute of Information and Communications Technology KoganeiTokyo 184-8795Japan

Downward transport of stratospheric air into the troposphere(identified as stratospheric intrusions)could potentially modify the radiation budget and chemical of the Earth's surface *** the highest and largest plateau on earth,the Tibetan Plateau including the Himalayas couples to global climate,and has attracted widespread attention due to rapid warming and cryospheric *** studies recognized strong stratospheric intrusions in the Himalayas but are poorly understood due to limited direct evidences and the complexity of the meteorological dynamics of the third ***^(35)S is a radioactive isotope predominately produced in the lower stratosphere and has been demonstrated as a sensitive chemical tracer to detect stratospherically sourced air mass in the planetary boundary ***,we report 6-month(April–September 2018)observation of^(35)S in atmospheric sulfate aerosols(^(35)SO_(4)^(2-))collected from a remote site in the Himalayas to reveal the stratospheric intrusion phenomenon as well as its potential impacts in this *** the sampling campaign,the^(35)SO_(4)^(2-)concentrations show an average of 1,070±980 atoms/m^(3).In springtime,the average is 1,620±730 atoms/m^(3),significantly higher than the global existing data measured so *** significant enrichments of^(35)SO_(4)^(2-)measured in this study verified the hypothesis that the Himalayas is a global hot spot of stratospheric intrusions,especially during the springtime as a consequence of its unique geology and atmospheric *** combined with the ancillary evidences,e.g.,oxygen-17 anomaly in sulfate and modeling results,we found that the stratospheric intrusions have a profound impact on the surface ozone concentrations over the study region,and potentially have the ability to constrain how the mechanisms of sulfate oxidation are affected by a change in plateau atmospheric properties and *** study provides new observational constraints on stra

关键词： Himalayas Stratospheric intrusions Cosmogenic^(35)SO_(4)^(2-) Ozone Atmospheric oxidation