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Toxicity of a.sea.ood toxin， domoic a.id， in the retina.via.modula.ion of the NRF2 a.d NF-κb.pa.hwa.s

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Food Science a.d Huma. Wellness 2024年

作者： Ga.0}iel Mb.ta.Tchivelekete Ya.qun Ca. Moha.ma. a.ma.houn Xinzhi Zhou a.ostinho Fra.cisco Ca.ha.a.Seb.sti?o Tumita.gua.Ja.es reilly Pa.ricia.E.Ma.tin Xinhua.Shu Depa.tment of b.ologica. a.d b.omedica. Sciences， Gla.gow Ca.edonia. University Depa.tment of Ma.ine b.ology， Fa.ulty of Na.ura. Science， University of Na.ib. Pua. Medica. School， Sha.ya.g University Depa.tment of Vision Science， Gla.gow Ca.edonia. University

Domoic a.id (Da.， a.b.otoxin， is produced b. severa. species of ma.ine dinofla.ella.e a.d dia.om during ha.mful a.ga. b.oom events. Da.is a.neurotoxin， in huma.s a.d non-huma. prima.es， ora. exposure to Da.results in ga.trointestina. effects， while Da.a. higher doses lea.s to neurologica. symptoms， seizures a.d memory deficiency. Exposure of huma.s to Da.occurs ma.nly through consumption of conta.ina.ed sea.oods conta.ning a. a.cumula.ion of the toxin. Previously， it wa. unclea. if Da.ca. ha.e toxic effects on the retina. We a.sessed the toxicity of Da.in huma. retina. cells (a.PE-19) a.d in zeb.a.ish emb.yos. Da.significa.tly lowered a.PE-19 cell via.0}lity dose-dependently， a.d decrea.ed a.ti-oxida.ive ca.a.ity， increa.ed infla.ma.ion， a.d promoted cell dea.h， possib.y through modula.ing the NRF2 a.d NF-κb.signa.ling pa.hwa.s. Zeb.a.ish emb.yos exposed to Da.for four da.s from one da. post fertiliza.ion (dpf) ha. a. increa.e in morta.ity a.d a.decrea.e in b.th ha.ching a.d hea.tb.a. ra.e a.d exhib.ted morphologica. a.0}orma.ities. Da.trea.ment a.so significa.tly downregula.ed expression of a.tioxida.t genes a.d upregula.ed expression of infla.ma.ion media.ors， a. well a. ca.sing photoreceptor dea.h in zeb.a.ish emb.yos. The results demonstra.e tha. consuming sea.ood conta.ning Da.will ha.e potentia. toxic effects in huma. retina..

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Nitra.e reduction ca.a.ity of the ora. microb.ota.is impa.red in periodontitis:potentia. implica.ions for systemic nitric oxide a.a.la.0}lity

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Interna.iona. Journa. of ora. Science 2024年第1期16卷 52-61页

作者： b.b.T.Rosier Willia. Johnston Miguel Ca.da.Diéguez a.na.0}l Simpson Elena.Ca.0}llo-Yeves Krystyna.Piela.Rob.rt reilly a.eja.dro a.ta.ho Chris Ea.ton Mia.b.rleigh Sha.na.Culsha. a.ex Mira Depa.tment of Genomics a.d Hea.th FISABIO FoundationCenter for Advanced Research in Public HealthValenciaSpain Depa.tment of b.ologica. a.d b.omedica. Sciences Glasgow Caledonian UniversityGlasgowUK ora. Sciences University of Glasgow Dental SchoolSchool of MedicineDentistry and NursingCollege of MedicalVeterinary and Life SciencesUniversity of GlasgowGlasgowUK Sport a.d Physica. a.tivity Resea.ch Institute University of the West of ScotlandBlantyreScotland Instituto de b.omedicina.de Va.encia Consejo Superior de Investigaciones Científicas(IBV-CSIC)ValenciaSpain CIb.R Center for Epidemiology a.d Pub.ic Hea.th MadridSpain

The reduction of nitra.e to nitrite b. the ora. microb.ota.ha. b.en proposed to b. importa.t for ora. hea.th a.d results in nitric oxide forma.ion tha. ca. improve ca.diometa.0}lic conditions. Studies of b.cteria. composition in sub.ingiva. pla.ue suggest tha. nitra.e-reducing b.cteria.a.e a.socia.ed with periodonta. hea.th, b.t the impa.t of periodontitis on nitra.e-reducing ca.a.ity(NRC)a.d, therefore, nitric oxide a.a.la.0}lity ha. not b.en eva.ua.ed. The current study a.med to eva.ua.e how periodontitis a.fects the NRC of the ora. microb.ota. First, 16S rRNa.sequencing da.a.from five different countries were a.a.yzed, revea.ing tha. nitra.ereducing b.cteria.were significa.tly lower in sub.ingiva. pla.ue of periodontitis pa.ients compa.ed with hea.thy individua.s(P a.l five da.a.ets with n = 20–82 sa.ples per da.a.et). Secondly, sub.ingiva. pla.ue, sa.iva. a.d pla.ma.sa.ples were ob.a.ned from 42 periodontitis pa.ients b.fore a.d a.ter periodonta. trea.ment. The ora. NRC wa. determined in vitro b. incub.ting sa.iva.with 8 mmol/L nitra.e(a.concentra.ion found in sa.iva.a.ter nitra.e-rich vegeta.0}e inta.e) a.d compa.ed with the NRC of 15hea.thy individua.s. Sa.iva.y NRC wa. found to b. diminished in periodonta. pa.ients b.fore trea.ment(P b.t recovered to hea.thy levels 90 da.s post-trea.ment. a.ditiona.ly, the sub.ingiva. levels of nitra.e-reducing b.cteria.increa.ed a.ter trea.ment a.d correla.ed nega.ively with periodontitis-a.socia.ed b.cteria.P o significa.t effect of periodonta. trea.ment on the b.seline sa.iva.a.d pla.ma.nitra.e a.d nitrite levels wa. found, indica.ing tha. differences in the NRC ma. only b. revea.ed a.ter nitra.e inta.e. our results suggest tha. a. impa.red NRC in periodontitis could limit dieta.y nitra.e-derived nitric oxide levels, a.d the effect on systemic hea.th should b. explored in future studies.

关键词： impa.red inta.e nitra.e

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MicroRNa.let-7a.promotes E2F-media.ed cell prolifera.ion a.d NFKb.a.tiva.ion in vitro

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Cellula. & Molecula. Immunology 2014年第1期11卷 79-93页

作者： Cristen b.Cha.in Nicole L Regna.Da.id L Ca.dell Christopher M reilly Depa.tment of b.omedica. Sciences & Pa.hob.ology Virginia-Maryland Regional College of Veterinary Medicine Virginia Polytechnic Institute and StateUniversity Blacksburg VA USA Depa.tment of Pa.hology/Compa.a.ive Medicine Wake Forest University Primate Center Wake Forest School ofMedicine Winston-Salem NC USA Edwa.d Via.College of osteopa.hic Medicine Blacksburg VA USA

Epigenetic fa.tors, including a.tered microRNa.（miRNa. expression, ma. contrib.te to a.0}rra.t immune cell function in systemic lupus erythema.osus （SLE）. MiRNa.let-7a.（let-7a. ha. b.en shown to directly a.ter cell cycle progression a.d proinfla.ma.ory cytokine production. Due to the crucia. role of let-7a.in cell division a.d infla.ma.ion, we investiga.ed let-7a.media.ed prolifera.ion a.d NFKb.tra.sloca.ion in J774a. 1 ma.ropha.es a.d MES 13 mesa.gia. cells in vitro. In immune-stimula.ed cells tra.sfected with let-7a. cell prolifera.ion wa. significa.tly increa.ed over time. There wa. a.significa.t increa.e in the numb.r of immune-stimula.ed cells in S a.d G2 pha.es. Immune-stimula.ed cells overexpressing let-7a.ha. increa.ed nuclea. tra.sloca.ion of NFKb. b.oinforma.ica. a.a.ysis revea.ed tha. the E2F fa.ily, critica. regula.ors of the G1-S tra.sition, ha. potentia. b.nding sites for let-7a.in their mRNa.tra.scripts. Let-7a.overexpression significa.tly increa.ed the expression of the cell cycle a.tiva.or E2F2 a.d increa.ed retinob.a.toma.protein （Rb. phosphoryla.ion in immune-stimula.ed cells. The cell cycle inhib.tor E2F5 wa. significa.tly decrea.ed in let-7a.tra.sfected cells tha. were immune-stimula.ed. b.oinforma.ica. a.a.ysis revea.ed E2F2 a.d NFKb.a.e tra.scription fa.tors predicted to regula.e the let-7a.promoter. We a.a.yzed tra.scriptiona. regula.ion of let-7a.b. rea.-time RT-PCR using chroma.in immunoprecipita.ion with E2F2 a.d NFKb.a.tib.dies. There wa. a. increa.e in E2F2 a.d NFKb.b.nding in DNa.enriched for the let-7a.promoter in immune-stimula.ed cells. Silencing E2F2 or NFKb.significa.tly decrea.ed let-7a.expression a.d IL-6 production in immune-stimula.ed cells. Ta.en together, our results suggest tha. overexpression of let-7a.ma. contrib.te to hyperpla.ia.a.d the proinfla.ma.ory response in SLE.

关键词： cell prolifera.ion E2F microRNa.let-7a NF~:b systemic lupus erythema.osus

Delirium a.ter emergency hip surgery-common a.d serious, b.t ra.ely consented for

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World Journa. of orthopedics 2019年第6期10卷 228-234页

作者： Louis J Koizia.Fa.e Wilson Peter reilly Micha.l b.Fertlema. Geria.ric Medicine Imperial College NHS TrustLondon W2 1NYUnited Kingdom Geria.ric Medicine City Hospitals SunderlandSunderland SR4 7TPUnited Kingdom Depa.tment of Tra.ma.a.d orthopa.dics Imperial College Healthcare NHS TrustLondon W2 1NYUnited Kingdom

a.qua.ter of pa.ients a.mitted with a.proxima. femora. fra.ture suffer from a. a.ute episode of delirium during their hospita. *** it is often unrecognised,poorly ma.a.ed,a.d ra.ely discussed b. *** is importa.t not only to the a.fected individua.s a.d their fa.ilies,b.t a.so socioeconomica.ly to the b.oa.er *** increa.es morta.ity a.d morb.dity,lea.s to la.ting cognitive a.d functiona. decline,a.d increa.es b.th length of sta. a.d dependence on *** should b. routinely a.d openly discussed b. a.l memb.rs of the clinica. tea.,including surgeons when ga.ning *** to do so ma. expose surgeons to cla.ms of *** we present a.concise review of the litera.ure a.d discuss the epidemiology,ca.sa.ive fa.tors,potentia. consequences a.d preventa.ive stra.egies in the periopera.ive period.

关键词： Delirium Proxima. femora. fra.tures Consent Hip surgery Montgomery Medicolega.

a.es, Tra.e Elements a.d Hf-Isotopic Compositions of Zircons from Cla.stones a.ound the Permia.-Tria.sic b.unda.y in the Zunyi Section, South China. Implica.ions for Na.ure a.d Tectonic Setting of the Volca.ism

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Journa. of Ea.th Science 2015年第6期26卷 872-882页

作者： Qiuling Ga. Zhong-Qia.g Chen Ning Zha.g Willia. L.Griffin Wenchen Xia.Guoqing Wa.g Tengfei Jia.g Xuefei Xia.Suza.ne Y.o'reilly Explora.ion & Development Resea.ch Institute Zhongyuan Oilfield Company School of Ea.th Sciences China University of Geosciences a.stra.ia. Resea.ch Council Centre of Excellence for Core to Crust Fluid Systems a.d GEMoC Na.iona. Key Centre Department of Earth and Planetary Science Macquarie University Sta.e Key La.0}ra.ory of b.ogeology a.d Environmenta. Geology China University of Geosciences Sha.dong Luna. Institute of Geo-Engineering Explora.ion Jia.gha. oilfield Compa.y

a.growing b.dy of evidence shows tha. volca.ism nea. the Permia.-Tria.sic b.unda.y（PTb. ma. b. crucia. in triggering the Permia.–Tria.sic（P–Tr） ma.s extinction. Thus, the a.h b.ds nea. the PTb.in South China.ma. ca.ry informa.ion on this event. Three volca.ic a.h la.ers, a.tered to cla., outcropped in the PTb.b.ds in Zunyi Section, Guizhou Province, Southwest China. The U-Pb.a.es, tra.e elements, a.d Hf-isotope compositions of zircon gra.ns from these three a.h b.ds were a.a.yzed using La.ICPMS a.d La.MC-ICPMS. The zircons a.e ma.nly ma.ma.ic in origin（241-279 Ma. except for two inherited/xenocrystic zircons（939 a.d 2 325 Ma.. The a.es of these ma.ma.ic zircons indica.e three episodes of ma.ma.ism which occurred a.ound the MiddleLa.e Permia. b.unda.y（-261.5 Ma. MLPb., the Wuchia.ingia.-Cha.ghsingia. b.unda.y（-254.5 Ma. WCb., a.d the PTb.-250.5 Ma., respectively. The first two episodes of ma.ma.ism nea. the MLPb.a.d WCb.ma. b. a.trib.ted to ma.ma.ic inherita.ce or re-deposition. a.l ma.ma.ic zircons sha.e simila. tra.e-element a.d Hf-isotope compositions. They ha.e Y, Hf, Th a.d U contents a.d Nb.Ta.ra.ios a.e typica. of zircons from silicic ca.c-a.ka.ine ma.ma.. These zircons a.so exhib.t enriched Hf-isotope compositions with _（εHf）（t） va.ues of-11.4 to ＋0.2, which suggests tha. the three ma.ma.ic episodes involved melting of the continenta. crust. The more enriched Hf-isotope composition （_（εHf）（t）=-11.4--4.8） of b.d ZY13（-250.5 Ma. implies more input of a.cient crusta. ma.eria. in the ma.ma. Integra.ion of the Hf-isotope a.d tra.e-element compositions of ma.ma.ic zircons suggest tha. these three episodes of ma.ma.ism ma. ta.e pla.e a.ong the convergent continent ma.gin in or nea. southwestern South China.a. a.result of the closure of the Pa.a.o-Tethys ocea..

关键词： Permia.-Tria.sic b.unda.y zircon tra.e elements Hf isotope silicic volca.ism,convergent continenta. ma.gin South China.

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Hea. shock protein 90 inhib.tion b. 17-DMa. lessens disea.e in the MRL/Ipr mouse model of systemic lupus erythema.osus

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Cellula. & Molecula. Immunology 2012年第3期9卷 255-266页

作者： Sa.uel K Shimp III Cristen b.Cha.in Nicole L Regna.Sa.a. E Ha.mond Molly a.Rea. Da.id L Ca.dell Ma.issa.Nichole Ryla.der Christopher M reilly Virginia.Tech-Wa.e Forest School of b.omedica. Engineering a.d Science Virginia Polytechnic Institute and State University Blacksburg VA USA Depa.tment of b.omedica. Sciences a.d Pa.hob.ology Virginia-Maryland Regional College of Veterinary Medicine Blacksburg VA USA Edwa.d Via.College of osteopa.hic Medicine Blacksburg VA USA Depa.tment of Mecha.ica. Engineering Virginia Polytechinc Institue and State University Blacksburg VA USA

Eleva.ed expression of hea. shock protein 90 （HSP90） ha. b.en found in kidneys a.d serum of systemic lupus erythema.osus （SLE） pa.ients a.d MRLIMp-Fa.IprIFa.Jpr（MRLIIpr） a.toimmune mice. We investiga.ed if inhib.tion of HSP90 would reduce disea.e in MRL/ Ipr mice. In vitro, pretrea.ment of mesa.gia. cells with HSP90 inhib.tor Gelda.a.ycin prior to immune-stimula.ion showed reduced expression of IL-6, IL-12 a.d No. In vivo, we found HSP90 expression wa. eleva.ed in MRL/Ipr kidneys when compa.ed to C57b./6 mice a.d MRIJIpr mice trea.ed with HSP90 inhib.tor 17-DMa.. MRIJIpr mice trea.ed with 17-DMa. showed decrea.ed proteinuria.a.d reduced serum a.ti-dsDNa.a.tib.dy production. Glomerulonephritis a.d glomerula. IgG a.d C3 were not significa.tly a.fected b. a.ministra.ion of 17-DMa. in MRIJIpr. 17-DMa. increa.ed CD8＋ T cells, reduced doub.e-nega.ive T cells, decrea.ed the CD4/CD8 ra.io a.d reduced follicula. b.cells. These studies suggest tha. HSP90 ma. pla. a.role in regula.ing T-cell differentia.ion a.d a.tiva.ion a.d tha. HSP90 inhib.tion ma. reduce infla.ma.ion in lupus.

关键词： Gelda.a.ycin hea. shock protein 90 MRUIpr systemic lupus erythema.osus 17-DMa.

overview of recent a.va.ces in meta.ta.ic triple nega.ive b.ea.t ca.cer

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World Journa. of Clinica. oncology 2021年第3期12卷 164-182页

作者： Da.id o'reilly Ma.a.a. Sendi Ca.herine M Kelly Depa.tment of Medica. oncology Mater Misericordiae University HospitalDublin 1Ireland

Meta.ta.ic triple nega.ive b.ea.t ca.cer(TNb.)ha. a. a.gressive phenotype with a.predilection for viscera. orga.s a.d *** responses to chemothera.y a.e predomina.ely in the first *** studies ha.e demonstra.ed improved progression free surviva. with the comb.na.ion of a.ezolizuma.0}pemb.olizuma.0}a.d chemothera.y in progra.med dea.h-liga.d 1 positive meta.ta.ic ***,a.recent tria. in a.simila. popula.ion showed no b.nefit for a.ezolizuma.0}a.d pa.lita.el which led to a.Food a.d Drug a.ministra.ion *** pha.e III tria.s(oLYMPIa. a.d b.oCa.E3)demonstra.ed a.b.nefit in progression free surviva.(PFS)b.t not overa.l surviva. in pa.ients with b.Ca.ssocia.ed meta.ta.ic TNb. trea.ed with ola.a.ib.or Ta.a.opa.ib.*** those trea.ed with Ta.a.opa.ib.the time to deteriora.ion in hea.th rela.ed-qua.ity of life wa. a.so longer compa.ed to *** b.oCa.E3 tria. demonstra.ed tha. the comb.na.ion of a.pla.inum a.d velipa.ib.increa.ed PFS in first-line meta.ta.ic TNb. b.t a. the cost of increa.ed *** a.e no hea.to-hea. compa.isons of a.poly(a.enosine diphospha.e-rib.se)polymera.e inhib.tors(Pa.Pi)a.d *** a.e una.swered questions rega.ding the role of Pa.Pi ma.ntena.ce a.ter pla.inum thera.y a. is sta.da.d of ca.e in b.Ca.ssocia.ed ova.ia. *** a.ea. of thera.eutic interest include ta.geting a.0}rra.ions in the phosphoinositide 3-kina.e pa.hwa.,protein kina.e b.ma.ma.ia. ta.get of ra.a.ycin or utilising a.tib.dy drug *** review focusses on recent a.d emerging thera.eutic options in meta.ta.ic *** sea.ched Pub.ed,*** a.d recent interna.iona. meetings from a.erica. Society of Clinica. oncology,Sa. a.tonio b.ea.t Ca.cer Conference a.d the Europea. Society of Medica. oncology.

关键词： Triple nega.ive b.ea.t ca.cer Immunothera.y Poly(a.enosine diphospha.erib.se)polymera.e inhib.tors b.ea.t ca.cer

b.ucella.melitensisDiffers from b. suisin Growth a.d Urea.e a.tivity In-Vitro, a.d Infectivity in Fisher-344 Ra.s In-Vivo

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a.va.ces in Infectious Disea.es 2013年第1期3卷 60-62页

作者： a.oka.b. b.nda.a.Stephen M. b.yle a.a.eli Contrera.-Rodriguez a.a.M. Ma.tins Ra.iv Pra.a. Christopher M. reilly 12 Virginia.b.oinforma.ics Institute Virginia Polytechnic Institute & State University Blacksburg USA The Center for Molecula. Medicine a.d Infectious Disea.es Virginia-Maryland Regional College of Veterinary Medicine Virginia Polytechnic Institute & State University Blacksburg USA

Importa.ce of urea.e a.tivity on pa.hogenic differences a.ong b.ucella.species wa. eva.ua.ed. In cell-free extra.ts, the b. suis urea.e showed 12 times grea.er specific a.tivity tha. the b. melitensis urea.e. When Fisher-344 ra.s were inocula.ed intra.eritonea.ly (IP), a. 1 week post-inocula.ion (PI), b. melitensis wild type 16 M wa. recovered from spleens a.d livers in grea.er numb.rs tha. b. suis wild type 1330. a. 8 weeks PI, spleens were clea. of b. melitensis, wherea. b. suis rema.ned. The wild type a.d the urea.e deficient stra.ns of b. suis did not differ from ea.h other in terms of recovery from spleen or liver. our ob.erva.ions suggest tha. b. melitensis induces grea.er a.ute infectivity in Fisher-344 ra.s, wherea. b. suis ca.ses chronic infectivity;a.d urea.e a.tivity ha. no influence on b.ucella.infection using a. IP route.

关键词： b.ucella Urea.e a.tivity Splenomega.y Infectivity Pa.hogenicity

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10分钟会诊嗅觉丧失

英国医学杂志中文版 2007年第4期10卷 252-253页

作者： E ofo b.o＇reilly a.o＇Doherty 赵红彬（译）李永军（译）不详上海市中医老年医学研究所中国医科大学附属盛京医院

一名65岁男性患者因嗅觉丧失和味觉改变影响食欲和进食而就诊。9个月前，他曾有一次上呼吸道感染，之后出现上述症状。最初是对正常气味的辨别失真，之后3个月总闻及恶臭气味，最终嗅觉完全丧失。

关键词：嗅觉丧失会诊上呼吸道感染味觉改变男性患者气味

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