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Co-nanoencapsulated meloxicam and curcumin improves cognitive impairment induced by amyloid-beta through modulation of cyclooxygenase-2 in mice

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Neural Regeneration Research 2021年第4期16卷 780-786页

作者： Maria Eduarda Ziani Gutierrez Anne Suély Pinto Savall Edina da Luz Abreu kelly ayumi nakama Renata Bem Dos Santos Marina Costa Monteiro Guedes Daiana SilvaÁvila Cristiane Luchese Sandra Elisa Haas Caroline Brandão Quines Simone Pinton Postgraduation Program in Biochemistry Federal University of Pampa(UNIPAMPA)UruguaianaRSBrazil Postgraduation Program in Pharmaceutical Science Federal University of Pampa(UNIPAMPA)UruguaianaRSBrazil Postgraduation Program in Biochemistry and Bioprospecting Federal University of Pelotas(UFPEL)Capão do LeãoRSBrazil

Alzheimer’s disease is a progressive brain disorder and complex mechanisms are involved in the physiopathology of Alzheimer’s ***,there is data suggesting that inflammation plays a role in its development and ***,some non-steroidal antiinflammatory drugs,such as meloxicam,which act by inhibiting cyclooxygenase-2 have been used as neuroprotective agents in different neurodegenerative disease *** purpose of this study was to investigate the effects of co-nanoencapsulated curcumin and meloxicam in lipid core nanocapsules(LCN)on cognitive impairment induced by amyloid-beta peptide injection in *** were prepared by the nanoprecipitation *** Swiss mice received a single intracerebroventricular injection of amyloid-beta peptide aggregates(fragment 25–35,3 nmol/3μL)or vehicle and were subsequently treated with curcumin-loaded LCN(10 mg/kg)or meloxicam-loaded LCN(5 mg/kg)or meloxicam+curcumin-co-loaded LCN(5 and 10 mg/kg,respectively).Treatments were given on alternate days for 12 days(i.e.,six doses,once every 48 hours,by intragastric gavage).Our data showed that amyloid-beta peptide infusion caused long-term memory deficits in the inhibitory avoidance and object recognition tests in *** the inhibitory avoidance test,both meloxicam and curcumin formulations(oil or co-loaded LCN)improved amyloid-beta-induced memory impairment in ***,only meloxicam and curcumin-co-loaded LCN attenuated non-aversive memory impairment in the object recognition ***,the beneficial effects of meloxicam and curcuminco-loaded LCN could be explained by the anti-inflammatory properties of these drugs through cortical cyclooxygenase-2 *** study suggests that the neuroprotective potential of meloxicam and curcumin co-nanoencapsulation is associated with cortical cyclooxygenase-2 *** study was approved by the Committee on Care and Use of Experimental Animal Resources,the Federal University of Pampa,Brazil(app

关键词： Alzheimer’s disease curcumin cyclooxygenase-2 lipid core nanocapsules meloxicam memory rats inflammation

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A gigaparsec-scale local void and the Hubble tension

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Science China(Physics,Mechanics & Astronomy) 2020年第9期63卷 7-15页

作者： QianHang Ding Tomohiro nakama Yi Wang Department of Physics The Hong Kong University of Science and TechnologyHong KongChina Jockey Club Institute for Advanced Study The Hong Kong University of Science and TechnologyHong KongChina

We explore the possibility of using a gigaparsec-scale local void to reconcile the Hubble *** a gigaparsec-scale void can be produced by multi-stream inflation where different parts of the observable universe follow different inflationary *** trajectories become different parts of the observable universe after inflation,when these scales return to the *** these trajectories have different e-folding numbers,these parts of the universe have different energy densities,possibly creating a local large *** impacts of such a void for cosmological observations are studied,especially those involving supernovae,Baryon Acoustic Oscillations(BAO)and the kinetic Sunyaev-Zel’dovich(kSZ)*** show that with the presence of the void,supernovae observations may be more consistent with the *** also estimate the impacts of a local large void on BAO *** addition,we show that a local large void and hence its capabilities to ease the Hubble tension is limited by the kSZ *** a benchmark model,a 1.7 Gpc scale void with boundary width 0.7 Gpc and density contrast-0.14 may ease the Hubble tension,evading the kSZ limit.

关键词： Hubble tension void cosmology inflation

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Screening of agonistic activities against four nuclear receptors in wastewater treatment plants in Japan using a yeast two-hybrid assay

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Journal of Environmental Sciences 2011年第1期23卷 125-132页

作者： Daisuke Inoue Koki nakama Kazuko Sawada Taro Watanabe Hisae Matsui Kazunari Sei Tsuyoshi Nakanishi Michihiko Ike Division of Sustainable Energy and Environmental Engineering Osaka University2-1 YamadaokaSuitaOsaka 565-0871Japan Laboratory of Hygienic Chemistry and Molecular Toxicology Gifu Pharmaceutical University5-6-1 Mitahora-higashiGifu 502-8585Japan

To assess the potential endocrine disruptive effects through multiple nuclear receptors （NRs）, especially non-steroidal NRs, in municipal wastewater, we examined the agonistic activities on four NRs （estrogen receptor α, thyroid hormone receptor α, retinoic acid receptor ct and retinoid X receptor α） of untreated and treated wastewater from municipal wastewater treatment plants （WWTPs） in Japan using a yeast two-hybrid assay. Investigation of the influent and effluent of seven WWTPs revealed that agonistic activities against steroidal and non-steroidal NRs were always detected in the influents and partially remained in the effluents. Further investigation of four WWTPs employing conventional activated sludge, pseudo-anoxic-oxic, anoxic-oxic and anaerobic-anoxic-oxic processes revealed that the ability to reduce the agonistic activity against each of the four NRs varies depending on the treatment process. These results indicated that municipal wastewater in Japan commonly contains endocrine disrupting chemicals that exert agonistic activities on steroidal and non-steroidal NRs, and that some of these chemicals are released into the natural aquatic environment. Although the results obtained in yeast assays suggested that measured levels of non-steroidal NR agonists in the effluent of WWTPs were not likely to cause any biological effect, further study is required to assess their possible risks in detail.

关键词： agonistic activity endocrine disrupting chemicals non-steroidal nuclear receptor wastewater treatment plants

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Approaches for representing hydro-mechanical coupling between sub-surface excavations and argillaceous porous media at the ventilation experiment, Mont Terri

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Journal of Rock Mechanics and Geotechnical Engineering 2013年第2期5卷 85-96页

作者： Alexander Bond Alain Millard Shigeo nakama Chengyuan Zhang Benoit Garritte Quintessa Ltd. Chadwick House Birchwood Park Warrington Cheshire A3 6AEUK Commissariatà l'Energie Atomique YvetteFrance Japan Atomic Energy Agency (JAEA) Tokai Japan Institute of Rock and Soil Mechanics Chinese Academy of Sciences Universidad Politcnica de Catalunya Barcelona Spain

At the Mont Terri Underground Research Laboratory （Switzerland）, a field-scale investigation has been conducted in order to investigate the hydro-mechanical and chemical perturbations induced in the argilla- ceous formation by forced ventilation through a tunnel. This experiment has been selected to be used for processing model development and validation in the international project DECOVALEX-2011. The con- ceptual and mathematical representation of the engineered void, which itself forms a major part of the experiment and is not simply a boundary condition, is the subject of this paper. A variety of approaches have been examined by the contributors to DECOVALEX and a summary of their findings is presented here. Two major aspects are discussed. Firstly, the approaches for the treatment of the surface condition at the porous media/tunnel interface are examined, with two equivalent but differing formulations successfully demonstrated. Secondly, approaches for representing the tunnel with associated air and water vapour movement, when coupled with the hydro-mechanical （HM） representation of the porous medium, are also examined. It is clearly demonstrated that, for the experimental conditions of the ventilation experiment （VE） that abstracted physical and empirical models of the tunnel, can be used successfully to represent the hydraulic behaviour of the tunnel and the hydraulic interaction between the tunnel and the surrounding rock mass.

关键词： Tunnel Water vapour Hydro-mechanical (HM) coupling Numerical modelling Mont Terri Underground Research Laboratory (URL) Ventilation experiment (VE) Argillite

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Distribution characteristics of polychlorinated biphenyls (PCBs) in coastal areas of Okinawa Island,Japan

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Chinese Journal of Oceanology and Limnology 2007年第3期25卷 247-253页

作者： M.A.SHEIKH F.nakama T.OOMORI Marine and Environmental Science Graduate School of Engineering and Science University of the Ryukyus 1 Senbaru Nishihara-Town Okinawa 903-0213 Japan Detachment 3 Air Force Institute for Operational Health (AFIOH) Armstrong Laboratory Department of Chemistry Biology and Marine Science Faculty of Science University of the Ryukyus 1 Senbaru Nishihara-Town Okinawa 903-0213

Surface sediment and seawater samples were collected from coastal areas around Okinawa Island from September 2001 to May 2002. The samples were analyzed for total polychlorinated biphenyl (PCB) levels and homolog composition. The results show that total PCB levels ranged from 0.32 to 128.7 ng/g (dry wt.) in sediment and 1.59 to 2.48 ng/L in seawater. The levels exceed the Environmental Quality Standard (EQS) for water pollution of Japan. The distribution of PCB homolog showed different patterns in the sediments and seawaters. Penta-chlorobiphenyls (CBs) comprised the main congener group in seawater, while hexa-CBs were more abundant homologs in the sediments. The heavily contaminated sites featured higher CBs, including penta-CBs, hexa-CBs, and hepta-CBs, than those in less contaminated sites where tri-CBs dominated. This study provides current distribution and geochemical behavior of PCBs in the coastal areas around Okinawa Island.

关键词： PCBs Okinawa Island homolog coastal pollution

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Accounting for anisotropic effects in the prediction of the hydro-mechanical response of a ventilated tunnel in an argillaceous rock

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Journal of Rock Mechanics and Geotechnical Engineering 2013年第2期5卷 97-109页

作者： Alain Millard Alex Bond Shigeo nakama Chengyuan Zhang Jean-Dominique Barnichon Benoit Garitte Commissariatà l'Energie Atomique et aux Energies Alternatives Gif-sur-Yvette France Quintessa Ltd. Chadwick House Birchwood Park Warrington Cheshire WA3 6AE UK Japan Atomic Energy Agency Tokai Japan Insititute of Rock and Soil Mechanics Chinese Academy of Sciences Institute for Nuclear Radioprotection and Safety Fontenay-aux-roses France Universidad Politécnica de Catalunya Barcelona Spain

In order to investigate the hydro-mechanical （HM） and chemical perturbations induced in an argillaceous formation by forced ventilation during the operational period of a nuclear waste repository, a specific experiment has been performed in a tunnel, at Mont Terri Underground Research Laboratory （URL） in Switzerland. This experiment has been selected in the international project DECOVALEX for model vali- dation and the numerical simulation of this ventilation experiment （VE） is the object of the present paper. Since the argillaceous rock exhibits anisotropic properties, particular attention is given to the evaluation of the effects of various anisotropic features on the predicted results. In situ measurements such as relative humidity （RH）, global water mass extracted, pore water pressure, water content, and relative displace- ments are compared to predictions using both isotropic and anisotropic parameters. Water permeability anisotropy is shown to be the most influencing parameter by far, whereas in situ stress anisotropy has an effect only during the excavation phase. The anisotropy for mechanical parameterization has also some influence, in particular through HM couplings. These HM couplings have the potential to be very significant in terms of providing confidence in describing the experimental observation, and should be considered for further investigation.

关键词： Hydro-mechanical (HM) coupling Numerical modelling Anisotropy Mont Terri Underground Research Laboratory (URL) Ventilation experiment (VE) Argillite

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Reactive and non-reactive transport modelling in partially water saturated argillaceous porous media around the ventilation experiment,Mont Terri

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Journal of Rock Mechanics and Geotechnical Engineering 2013年第1期5卷 44-57页

作者： Alexander Bond Steven Benbow James Wilson Alain Millard Shigeo nakama Myles English Christopher McDermott Benoit Garitte Quintessa Ltd. Chadwick House Birchwood Park Warrington Cheshire WA3 6AE UK Commissariat à l'Energie Atomique Japan Atomic Energy Agency (JAEA) University of Edinburgh Universidad Politécnica de Catalunya

At Mont Terri Underground Research Laboratory （URL） Switzerland, a specific experiment has been per- formed in a tunnel, in order to investigate the hydro-mechano-chemical （HMC） perturbations induced in the argillaceous formation by forced ventilation. This experiment has been selected in the international project DECOVALEX to be used for process model development and validation. The numerical simula- tion of the geochemical response to the ventilation experiment （VE） is the object of the present paper, focusing on the transport of chloride as a conservative species and sulphate as a reactive species. Uti- lising the validated hydro-mechanical （HM） results from earlier steps of the DECOVALEX task, reactive and non-reactive transport models, incorporating the current understanding of the geochemistry at the site, were successfully constructed for the whole experimental period. The associated parametric and process uncertainty analyses clearly demonstrate that the basic HM understanding must be sound. How- ever, to demonstrate this degree of robustness, the explicit inclusion of process representations of water desaturation, liquid vaporisation, species exclusion porosity, and redox processes, is required.

关键词： Reactive transportHydro-mechanical (HM) couplingNumerical modellingMont Terri Underground ResearchLaboratory (URL)Ventilation experiment (VE)ArgilliteChlorideSulphate

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Analysis of hydro-mechanical processes in a ventilated tunnel in an argillaceous rock on the basis of different modelling approaches

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Journal of Rock Mechanics and Geotechnical Engineering 2013年第1期5卷 1-17页

作者： B.Garitte A.Bond A.Millard C.Zhang C.Mcdermott S.nakama A.Gens Universidad Politécnica de Catalunya Quintessa WarringtonUK Commissariat à l'Energie Atomique Gif-sur-Yvette France Chinese Academy of Sciences ECOSSE University of Edinburgh Japan Atomic Energy Agency

In this paper, a modelling benchmark exercise from the DECOVALEX-2011 project is presented. The bench- mark is based on the performance and results of a laboratory drying test and of the ventilation experiment （VE） carried out in the Mont Terri Underground Rock Laboratory （URL）. Both tests involve Opalinus clay. The work aims at the identification, understanding and quantification of mechanisms taking place during the ventilation of a gallery in argillaceous host rocks on one hand and at investigating the capacity of different codes and individuals to reproduce these processes on the other hand. The 4-year in situ VE took place in a 1.3 m diameter unlined tunnel and included two resaturation-desaturation cycles. The test area was equipped with over one hundred sensors （including the global water mass balance of the system, relative humidity （RH）, water content, liquid pressure, relative displacement and concentration of some chemical species） to monitor the rock behaviour during ventilation. The laboratory drying experiment, carried out before the VE, was designed to mimic the in situ conditions. The work was organized in a progressive manner in terms of complexity of the computations to be performed, geared towards the full hydro-mechano-chemical （HMC） understanding of the VE, the final objective. The main results from the modelling work reported herein are that the response of the host rock to ventilation in argillaceous rocks is mainly governed by hydraulic processes （advective Darcy flow and non-advective vapour diffu- sion） and that the hydro-mechanical （TM） back coupling is weak. A ventilation experiment may thus be regarded as a large scale-long time pump test and it is used to determine the hydraulic conductivity of the rock mass.

关键词： Hydro-mechanical (HM) couplingNumerical modellingMont Terri Underground Rock Laboratory(URL)Ventilation experiment (VE)ArgilliteWater permeability

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Numerical modeling for the coupled thermo-mechanical processes and spalling phenomena in sp Pillar Stability Experiment (APSE)

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Journal of Rock Mechanics and Geotechnical Engineering 2013年第1期5卷 58-72页

作者： T.Koyama M.Chijimatsu H.Shimizu S.nakama T.Fujita A.Kobayashi Y.Ohnishi Department of Urban Management Kyoto University Hazama Corporation Institute of Fluid Science Tohoku University Japan Atomic Energy Agency (JAEA) Faculty of Environmental and Urban Engineering Kansai University Kyoto University

In this paper, the coupled thermo-mechanical （TM） processes in the AEspoe Pillar Stability Experiment （APSE） carried out by the Swedish Nuclear Fuel and Waste Management Company （SKB） were simulated using both continuum and discontinuum based numerical methods. Two-dimensional （2D） and three- dimensional （3D） finite element method （FEM） and 2D distinct element method （DEM） with particles were used. The main objective for the large scale in situ experiment is to investigate the yielding strength of crystalline rock and the formation of the excavation disturbed/damaged zone （EDZ） during excavation of two boreholes, pressurizing of one of the boreholes and heating. For the DEM simulations, the heat flow algorithm was newly introduced into the original code. The calculated stress, displacement and temperature distributions were compared with the ones obtained from in situ measurements and FEM simulations. A parametric study for initial microcracks was also performed to reproduce the spalling phenomena observed in the APSE.

关键词： Coupled thermo-mechanical (TM)processesAspoe Pillar Stability Experiment (APSE)Excavation disturbed/damaged zone (EDZ)Finite element method (FEM)Distinct element method (DEM)

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Attenuation of periostin in retinal Müller glia by TNF-α and IFN-γ

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International Journal of Ophthalmology(English edition) 2019年第2期12卷 212-218页

作者： Ying-Qian Peng Man-Jing Cao Shigeo Yoshida Lu-Si Zhang Hui-Lan Zeng Jing-Ling Zou Yoshiyuki Kobayashi Takahito nakama Jing-Ming Shi Song-Bai Jia Ye-Di Zhou Department of Ophthalmology the Second Xiangya Hospital Central South University Hunan Clinical Research Center of Ophthalmic Disease Department of Ophthalmology Kyushu University Graduate School of Medical Sciences Department of Ophthalmology Kurume University School of Medicine

AIM: To investigate the regulation and mechanisms of periostin expression in retinal Müller glia, and to explore the relevance to retinal neovascularization. METHODS: The oxygen-induced retinopathy(OIR) mouse model and the human Moorfield/Institute of Ophthalmology-Müller 1(MIO-M1) cell line were used in the study. Immunofluorescence staining was used to determine the distribution and expression of periostin and a Müller glial cell marker glutamine synthetase(GS). Cytokines TNF-α and IFN-γ were added to stimulate the MIO-M1 cells. ShRNA was used to knockdown periostin expression in MIO-M1 cells. Quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR) was conducted to assess the mRNA expression of periostin. RESULTS: Immunofluorescence staining showed that periostin was expressed by MIO-M1 Müller glia. GS-positive Müller glia and periostin increased in OIR retinas, and were partially overlaid. The stimulation of TNF-α and IFN-γ reduced the mRNA expression of periostin significantly and dose-dependently in MIO-M1 cells. Knockdown of periostin reduced mRNA expression of vascular endothelial growth factor A(VEGFA) in MIO-M1 cells, while VEGFA expression was not changed in periostin knock-out OIR retinas. CONCLUSION: Müller glia could be one of the main sources of periostin in the retina, and might contribute to the pathogenesis of retinal neovascularization. Proinflammatory cytokines TNF-α and IFN-γ attenuate the periostin expression in retinal Müller glia, which provides a potential and novel method in treating retinal neovascular diseases.

关键词： TNF-α IFN-γ periostin Müller glia retinal neovascularization

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