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| 1 | Neuroprotective effects of INT-777 against Aβ1-42-induced cognitive impairment, neuroinflammation, apoptosis, and synaptic dysfunction in mice显示文摘OBJECTIVE To investigate the neuroprotective effects of TGR5 agonist INT-777 in the Aβ_(1-42)-treated mouse model of acute neurotoxicity.METHODS Cognitive impairment was induced by single intracerebroventricular injection of aggregated Aβ_(1-42)(410 pmol per mouse;5 μL)into the mouse brain in normal ICR mice.After3 d,INT-777(0.75,1.5 or 3.0 μg per mouse) was infused into the same site.Another 3 d later,the cognition function was evaluated by Morris water maze(MWM),novel objective recognition(NOR),and Y maze tests.Furthermore,the levels of TGR5,TNF-α,IL-1β,IL-6,NF-κB p65,Iba1,caspase 3,Bcl-2,Bax,PSD95,and synaptophysin in the hippocampus and frontal cortex were detected using Western blotting.Microglia activation in the hippocampal CA1,CA3 and DG regions and frontal cortex were detected by immunohistochemistry.TUNEL staining was used to detect the apoptotic cells.The number of spines in the hippocampal CA1,CA3 and DG regions and frontal cortex was detected by GolgiCox staining.RESULTS INT-777(1.5 or 3.0 μg per mouse) significantly ameliorated memory impairment in the Aβ_(1-42)-treated mice,evidenced by increased the time spent in the target quadrant(P<0.05),and the number of target crossings(P<0.05) in the MWM test,increased the discrimination index in the NOR test(P<0.05),and increased the number of correct choices(P<0.05,P<0.01) and decreased the latency(P<0.05) to enter the shock-free compartment in the Y-maze test.Importantly,this treatment reversed Aβ_(1-42)-induced TGR5 down-regulation(P<0.05,P<0.01),suppressed the increase of nuclear NF-κB p65(P<0.05,P<0.01) and mitigated neuroinflammation,evidenced by lower proinflammatory cytokines such as TNF-α(P<0.05),IL-1β(P<0.05),IL-6(P<0.05,P<0.01),and less Iba1-positive cells in the hippocampal CA1,CA3 and DG regions and frontal cortex(P<0.05,P<0.01) as well as the protein level of Iba1.INT-777(1.5 or3.0 μg per mouse) also pronouncedly suppressed apoptosis through the reduction of TUNEL-positive cells(P<0.05,P<0.01),decreased activation of caspase 3(P<0.05),increased ratio of Bcl-2/Bax(P<0.05,P<0.01),and ameliorated synaptic dysfunction via promoting dendritic spines generation(P<0.05,P<0.01) with the upregulation of PSD95(P<0.05) and synaptophysin proteins(P<0.05).CONCLUSION INT-777 has potent neuroprotective effects against Aβ_(1-42)-induced neurotoxicity,which suggests that the activation of TGR5 could be a novel and promising strategy for the treatment of AD. | WU Xian LYU Yang-ge DU Yi-feng CHEN Fang Miranda N REED HU Mei Vishnu SUPPIRAMANIAM TANG Su-su HONG Hao | 2018 | 中国药理学与毒理学杂志2018，32，9： | 6 |
| 2 | Efficient metallization of magnetite concentrate by reduction with agave bagasse as a source of reducing agents显示文摘The reduction behavior and metallization degree of magnetite concentrate with agave bagasse were investigated in an inert atmosphere.The effects of temperature,biomass content,and residence time on reduction experiments and metallization degree were investigated by X-ray diffraction and scanning electron microscopy.Compared with other types of biomass,agave bagasse had lower contents of nitrogen,sulfur,and ash.X-ray diffraction analysis showed that the metallization degree improved with increasing temperature and biomass content.Complete metallization was achieved at 1100℃ for 30 min with 65:35 and 50:50 ratios of the magnetite concentrate to the agave bagasse.These results demonstrate that agave bagasse promotes the efficient metallization of magnetite concentrate without the external addition of a reducing agent.Therefore,this biomass is a technical suitable alternative to replace fossil fuels in steelmaking. | Diana Cholico-González NoemíOrtiz Lara Mario Alberto Sánchez Miranda Ricardo Morales Estrella Ramiro Escudero García Carlos ALeón Patiño | 2021 | International Journal of Minerals,Metallurgy and Materials2021，28，4： | 2 |
| 3 | Semivariogram textural classification of JERS-1(FUYO-1) SAR data obtained over a flooded area of the Amazonian rainforest显示文摘 | Miranda F P Fonseca L E N Carr J R | 2000 | International Journal of Remote Sensing2000，19，3： | 1 |
| 4 | Lymphomas involving the breast:a study of 106 cases comparing localized and disseminated neoplasms显示文摘 | Talwalkar S S Miranda R N Valbuena J R | | 0，，09： | 1 |
| 5 | A bifunctional TPS- TPP enzyme from yeast confers tolerance to multiple and extreme abiotic-stress conditions in transgenic Arabidopsis显示文摘 | Miranda J A Avonce N Suarez R | 2007 | Planta2007，226，6： | 1 |
| 6 | Effects of plough pan development on surface hydrology and on soil physical properties in Southeastern Brazilian pla- teau显示文摘 | Bertolino Aria V F A Fernandes N F Miranda J P L | 2010 | J Hydro2010，393，12： | 1 |
| 7 | Clear cell sarcoma of ten-dons and aponeuroses: a review 显示文摘 | Dim D C Cooley L D Miranda R N | 2007 | Arch Pathol Lab Med2007，131，： | 1 |
| 8 | Hepatuc:yte growth factor/scatter factor (HGF/SF) is produced by human bone marrow stromal cells and promotes proliferation,adhesion and survival of human hematopoietic progenitor cells (CD34+)显示文摘 | Weimar LS Miranda N Muller EJ | 1998 | Exn Hematol1998，26，9： | 1 |
| 9 | Co-gasification study of biomass mixed with plastic wastes显示文摘 | PINTO F FRANCO C ANDRE R N MIRANDA M GULYURTLU I CABRITA I | 2002 | Fuel2002，81，3： | 1 |
| 10 | Regression of infancy hemangioma with recombinant IFN-alpha 2b显示文摘 | Garmendia G Miranda N Borroso S | 2001 | J Interferon Cytokine Res2001，21，1： | 1 |
| 11 | Breast implant-associated anaplastic large-cell lymphoma:long-term follow-up of 60patients显示文摘 | Miranda R N Aladily T N Prince H M | 2014 | J Clin Oncol2014，32，2： | 1 |
| 12 | Oral cancer susceptibility associated with the CYP1A1 and GSTM1 genotypesin Chilean individuals显示文摘 | Karina Cordero Iris Espinoza Dante Caceres Angela Roco Carla Miranda Valentina Squicciarini Paula Santander Kuen Lee Iván Saavedra Luis Qui?ones | 2010 | Oncology Letters2010，，3： | 1 |
| 13 | Efeito de aplicacao de molibdenio no numero de Azospirillum e na producao de Brachiaria decumbens显示文摘 | Miranda C H B Seiffert N F Dobereiner J | 1985 | Pesqui Agrppecu Bras1985，20，5： | 1 |
| 14 | Mercury contamination associated with artisanal gold mining on the island of Mindanao,the Philippines显示文摘 | APPLETON J D WILLIAMS T M BREWARD N APOSTOL A MIGUEL J MIRANDA C | 1999 | The Science of the Total Environment1999，228，： | 1 |
| 15 | The role of oxidative stress in the toxicity induces by amyloid beta-peptide in Alzheimer's disease显示文摘 | Miranda S Opazo C Larrondo L F Munoz F J Ruiz F Leigh- ton F Inestmsa N C | 2000 | Prog Neurobiol2000，62，6： | 1 |
| 16 | Filter Coated with Colloidal Silver for SER Spectroscopy显示文摘 | Neto N Muniz- Miranda M Sbrana G | 1995 | J Mol Struct1995，348，： | 1 |
| 17 | The Spanish organizational structure for organ donation: update 显示文摘 | Miranda B Canon J Cuende N | 2001 | Transplant Rev2001，15，1： | 1 |
| 18 | A bifunctional TPS–TPP enzyme from yeast confers tolerance to multiple and extreme abiotic-stress conditions in transgenic Arabidopsis显示文摘 | José A. Miranda Nelson Avonce Ramón Suárez Johan M. Thevelein Patrick Dijck Gabriel Iturriaga | 2007 | Planta2007，，6： | 1 |
| 19 | Talking trash about landfills: Using quantitative scoring schemes in landfill siting processes 显示文摘 | Miranda M L Miller J N Jacobs T L | 2000 | Journal of Policy Analysis and Management2000，19，1： | 1 |
| 20 | Nimotuzumab in combination with radiotherapy in high grade glioma patients: asingle institution experience显示文摘 | Solomon MT Miranda N Jorrin E | 2014 | Cancer Biol Ther2014，15，5： | 1 |
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