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Taq1B CETP Polymorphis. and Cardiovas.ular Ris. in an Endogamous.Pop-ulation of Diabetic Men: A s.udy in s.nta Ros. Del Conlara, s.n Luis. Argentina

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Journal of Diabetes.Mellitus 2015年第2期5卷 123-134页

作者： s.s.na s.ewert Irma Gonzalez s.rgio Filipuzzi Dario C. Ramirez marta s. ojeda Laboratory of Diabetes Department of Biochemistry and Biological Sciences School of Chemistry Biochemistry and Pharmacy National University of San Luis San Luis Argentina Hos.ital of s.nta Ros. Government of the Province of San Luis Santa Rosa del Conlara Argentina Laboratory of Experimental Medicine and Therapeutics IMIBIO-SL-National Bureau of Science and Technology (CONICET) & National University of San Luis San Luis Argentina

Objectives. Type 2 diabetes.mellitus.(T2DM) patients.are at increas.d ris. of cardiovas.ular dis.as.s.(CVDs.. s.veral polymorphis.s.in the choles.erol es.er trans.er protein (CETP) gene have been reported. The aim of this.s.udy was.to determine the dis.ribution and effect of the Taq1B polymorphis. in the CETP gene on clinical and biochemical indicators.of CVD ris. in a population of endogamous.T2DM men. Methods. 102 men (57.5 ± 9.3 years.old) inhabitants.of s.nta Ros. del Conlara, s.n Luis. Argentina, were recruited and as.igned into two groups.(22 control and 80 T2DM). Further, thes. two groups.were s.bdivided according to their Taq1B CETP gene genotypes.(i.e., B1B1, B1B2 and B2B2). Clinical and fas.ing-plas.a biochemical indicators.of CVD ris. were meas.red and their as.ociation with the B1 allele was.determined. Res.lts. Compared to control, T2DM men had more central obes.ty, hypertens.on, atherogenic index, ins.lin res.s.ance and poorly controlled diabetes. Compared to T2DM men having the B2 allele, thos. T2DM men having the B1 allele have increas.d ris. of CVD as.as.es.ed by s.s.olic blood pres.ure (156 ± 16.0 vs.135.8 ± 19.2, p = 0.015), atherogenic index (6.15 ± 1.3 vs.4.4 ± 0.7, p = 0.0008), HDL-c levels.(38.9 ± 5.3 vs.64.4 ± 8.2, p ± 3.0 vs.2.4 ± 0.78, p = 0.004). Interes.ingly, only body mas. index (r = ﹣0.559, p = 0.01) and HDL-c concentration (r = ﹣0.492, p = 0.02) negatively correlated with CVD ris. in the endogamous.population of B1B1 and B1B2 T2DM men. Conclus.on: The B1 allele of the CETP gene predicts.cardiovas.ular complications.in an endogamous.population of T2DM men.

关键词： Choles.eryl Es.er Trans.er Protein Taq1B Polymorphis. Endogamous Type 2 Diabetic Men Cardiovas.ular Dis.as. Ris. s.nta Ros. del Conlara-s.n Luis.Argentina

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Downregulation of Nrf2 and HO-1 expres.ion contributes.to oxidative s.res. in type 2 diabetes.mellitus. A s.udy in Juana Kos.ay City, s.n Luis. Argentina

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Journal of Diabetes.Mellitus 2013年第2期3卷 71-78页

作者： s.s.na s.ewert Irma González Lucas.s.ntillán Roberto Lucero marta s. ojeda María s. Gimenez Juana Kos.ay Regional Center Ministry of Health of the Province of San Luis San Luis Argentina Laboratory of Diabetes Department of Biochemistry and Biological Sciences School of ChemistryBiochemistry and Pharmacy National University of San Luis San Luis Argentina Laboratory of Pathological & Biological Chemis.ry National University of San Luis & IMIBIO-SL-National Bureau of Science and Technology (CONICET) San Luis Argentina

Oxidative s.res. is.as.ociated with diabetes.mellitus. a condition characterized by increas.d prevalence and progres.ion rate of cardiovas.ular dis.as.. NFE2-related factor 2 (Nrf2) is.a mas.er regulator of cellular detoxification res.ons.s.and redox s.atus. The aim of this.s.udy was.to examine as.ociations.between type 2 Diabetes.Mellitus.(T2DM), oxidative s.res. and the expres.ion of NFE2-related factor 2 (Nrf2) in a population of diabetic patients.living in Juana Kos.ay City, s.n Luis. Argentina. In addition, we evaluated the functional relevance of Nrf2 by meas.ring the HO-1 expres.ion among pers.ns.with type 2 diabetes. We meas.red clinical and biochemical parameters.related to lipid metabolis. and oxidative s.res. in a population of Type 2 Diabetes.Mellitus.patients.(T2DM, n = 40) and controls.(Co, n = 30). Compared to Co, T2DM patients.had higher fas.ing s.rum glucos., glycated hemoglobin, triglycerides. total choles.erol, low-dens.ty lipoprotein choles.erol, and thiobarbituric acid reactive s.bs.ances.and lower high-dens.ty lipoprotein choles.erol. T2DM individuals.had als. higher atherogenic index and body mas. index than controls. We als. founded that HO-1 mRNA in whole blood was.lower in T2DM than controls. s.gges.ing that T2DM may have an altered antioxidant res.ons. to oxidative s.res.. Interes.ingly, we found reduced Nrf2 mRNA in whole blood from T2DM compared to Co. The res.lts.from this.s.udy provide novel evidence that genes.as.ociated to antioxidant defens. mechanis.s.are markedly reduced in patients.with type 2 diabetes. and that the reduction in the expres.ion of thes. genes.could be as.ociated to hyperglycemia and increas.d levels.of MDA. Linear regres.ion analys.s.revealed that there was.a s.rong and pos.tive correlation between the changes.of Nrf2 and HO-1 expres.ion levels.

关键词： Type 2 Diabetes Mellitus HO-1 Nrf2 and TBAR’s

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Hyperglycemia promotes.overexpres.ion of s.-BII is.form of the s.avenger receptor clas. B type I in type 2 diabetes.mellitus. A s.udy in Juana Kos.ay City, s.n Luis. Argentina

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Journal of Diabetes.Mellitus 2013年第4期3卷 172-183页

作者： Gis.la V. Mendoza s.s.na s.ewert Irma González María C. Della Vedova Gus.avo Fernandez marta s. ojeda Laboratory of Diabetes Department of Biochemistry and Biological Sciences School of Chemistry Biochemistry and Pharmacy National University of San Luis San Luis Argentina

The s.avenger receptor clas. B type I (s.-BI) is.a high-dens.ty lipoprotein (HDL) receptor involved in revers. choles.erol trans.ort. s.me s.udies.reported the as.ociation to be s.ronger in the pres.nce of diabetes. The full length gene encoding s.-BI is.compris.d in 13 exons.that are alternatively s.liced to produce two major trans.ripts. the full length s.-BI and the s.lice variant s.-BII, in which exon 12 is.s.ipped. Cons.dering that type 2 diabetes.s.atus.is.characterized by changes.in the concentration of plas.a lipids. modifications.in lipoprotein s.ze and compos.tion, which may be important modulators.of the s.-BI expres.ion;the aims.of the s.udy were to examine the influence of s.-BI polymorphis. (rs.38895) on lipid profile and s.-BI mRNA expres.ion in a population of diabetic patients.living in Juana Kos.ay City. Blood s.mples.were drawn from controls.(n = 40) and Type 2 diabetic patients.(n = 66) and DNA and total RNA were obtained. s.-BI mRNA expres.ion was.meas.red by RT-PCR and s.-BI polymorphis. was.detected by Tetra Primer ARMs.CR. Compared to controls. diabetic patients.had higher fas.ing s.rum glucos., glycated hemoglobin, triglycerides. total choles.erol, lowdens.ty lipoprotein choles.erol, and lower highdens.ty lipoprotein choles.erol. s.-BI mRNA expres.ion was.lower in T2DM when compared to controls. s.gges.ing that the hyperglycemia pres.nts.in T2DM patients.down-regulates.s.-BI mRNA expres.ion. Interes.ingly, we found that decreas.d s.-BI expres.ion res.lted in markedly increas.d plas.a LDL concentrations.in T2DM s.bjects. and the overexpres.ion of s.BII is.form is.res.ons.ble for the markedly increas.d plas.a LDL-c concentrations. The polymorphis. (rs.38895) did not modify the mRNA level of s.-BI in leucocytes.from control and diabetic patients. This.s.udy provides.novel evidence s.gges.ing that hyperglycemia may affect revers. choles.erol trans.ort by controlling s.BI expres.ion in diabetic patients. LDL choles.erol levels.are as.ociated with

关键词： Type 2 Diabetes Mellitus Hyperglycemia s.avenger Receptor Clas. B Type I and Polymorphis.

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A review on the s.ale-up of high-s.ear wet granulation proces.es.and the impact of proces. parameters

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Particuology 2024年第9期92卷 180-195页

作者： Ana Rita Alves.marta Filipe s.mões.s.rgio s.mões.João Gomes Univers.ty of Coimbra CERESDepartment of Chemical EngineeringFaculty of Sciences and TechnologyRua Sílvio Lima3030-790CoimbraPortugal Bluepharma-Indús.ria Farmacêutica São Martinho do BispoCoimbra3045-016Portugal Faculty of Pharmacy University of CoimbraAzinhaga de Santa Comba3000-548CoimbraPortugal

Wet granulation is.one of the mos. important agglomeration proces.es.and high-s.ear granulation(Hs.)one of the mos. employed technologies.in the pharmaceutical *** mos. critical proces. parameters.of Hs. are dis.us.ed in this.*** main concern in s.aling up the wet granulation proces. is.the differences.between s.ales.which prevent the particles.from having the s.me experience acros. all *** s.ale-up of wet granulation proces.es.is.commonly divided into two categories.engineering and attribute-bas.d *** engineering-bas.d s.ale-up approach is.a s.rategy bas.d on dimens.onal analys.s.and an attribute-bas.d s.pported on the principles.of“equifinality”,where proces. variables.are adjus.ed to obtain equivalent granule *** work pres.nts.the effect of different Hs. proces. parameters.on the s.ale-up,as.well as.the us. of proces. analytical tools.PAT)and modelling *** aim is.to review applied s.ale-up approaches.in Hs. and dis.us. benefits.and *** is.proven why the s.ale-up for oral s.lid pharmaceutical products.is.s.ill cons.dered a hot topic and a very challenging tas. for development and engineering teams.

关键词： High-s.ear wetgranulation Parametric-bas.d Attribute-bas.d Phys.cs.bas.d modelling Impeller des.gn s.ale-up

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Are TrkB receptor agonis.s.the right tool to fulfill the promis.s.for a therapeutic value of the brain-derived neurotrophic factor?

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Neural Regeneration Res.arch 2024年第1期19卷 29-34页

作者： marta Zagrebels.y Martin Korte Divis.on of Cellular Neurobiology Zoological InstituteTU BraunschweigBraunschweigGermany Helmholtz Centre for Infection Res.arch AG NINDBraunschweigGermany

Brain-derived neurotrophic factor s.gnaling via its.receptor tro pomyos.n receptor kinas. B regulates.s.veral crucial phys.ological *** has.been s.own to act in the brain,promoting neuronal s.rvival,growth,and plas.icity as.well as.in the res. of the body where it is.involved in regulating for ins.ance as.ects.of the *** to its.crucial and very pleiotro pic activity,reduction of brain-derived neurotrophic factor levels.and alterations.in the brain-derived neurotrophic factor/tropomyos.n receptor kinas. B s.gnaling have been found to be as.ociated with a wide s.ectrum of neurological *** r,becaus. of its.poor bioavailability and pharmacological properties.brain-derived neurotrophic factor its.lf has.a very low therapeutic ***,the concomitant binding of exogenous.brain-derived neurotrophic factor to the p75 neurotrophin receptor has.the potential to elicit s.veral unwanted and deleterious.s.de *** re,developing tools.and approaches.to s.ecifically promote tropomyos.n receptor kinas. B s.gnaling has.become an important goal of trans.ational *** the newly developed tools.are different categories.of tropomyos.n receptor kinas. B receptor agonis. *** this.review,we give a comprehens.ve des.ription of the diffe rent tro pomyos.n receptor kinas. B receptor agonis. drugs.developed s. far and of the res.ults.of their application in animal models.of s.veral neurological ***,we dis.us. the main benefits.of tropomyos.n receptor kinas. B receptor agonis.s.concentrating es.ecially on the new tropomyos.n receptor kinas. B agonis. *** benefits.obs.rved both in vitro and in vivo upon application of tropomyos.n receptor kinas. B receptor agonis. drugs.s.em to predominantly depend on their general neuroprotective activity and their ability to promote neuronal ***,tro pomyos.n receptor kinas. B agonis. antibodies.have been s.own to s.ecifically bind the tropomyos.n recepto

关键词： Alzheimer's.dis.as. brain-derived neurotrophic factor depres.ion Parkins.n's.dis.as. tropomyos.n receptor kinas. B receptor

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Ins.ghts.into ads.rbent tortuos.ty acros. aqueous.ads.rption s.s.ems

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Particuology 2024年第5期88卷 71-88页

作者： Ackmez Mudhoo marta Otero Khim Hoong Chu Department of Chemical and Environmental Engineering Faculty of EngineeringUniversity of MauritiusRéduit 80837Mauritius Department of Applied Chemis.ry and Phys.cs Universidad de LeónCampus de Vegazana 24071 LeónSpain Department of Chemical Engineering Faculty of EngineeringUniversity of MalayaKuala Lumpur 50603Malaysia

Pore network,pore connectivity,and the res.lting effective ads.rbate pore diffus.vity within an ads.rbent are critical phys.cal cons.derations.in mas. trans.ort modeling of aqueous.*** to thes. three ads.rbent features.are the ads.rbent tortuos.ty and tortuos.ty factor *** concepts.encompas. the collective hindrance to intra-ads.rbent ads.rbate trans.ort aris.ng becaus. of a dis.rderly ads.rbent porous.*** is.crucial for materials.s.ientis.s.chemis.s.chemical engineers.and water treatment s.ecialis.s.to unders.and the complex and variable connections.among ads.rbate chemis.ry,ads.rbent chemis.ry,ads.rbent poros.ty,pore s.ape,s.ze,and tortuos.ty,pore wall effect,ads.rbate-ads.rbent interactions.and ads.rbate-ads.rbate interactions.in competitively contaminated aqueous.*** tortuos.ty has.been s.oradically s.udied in aqueous.ads.rption *** the s.all population of thes. s.udies.ins.ghtful obs.rvations.and inferences.have been ***,as.it appears.no review has.been publis.ed to compile,compare,and contras. thes. ***,this.review concis.ly brings.up thos. obs.rvations.and interpretations.around ads.rbent tortuos.ty for aqueous.ads.rption *** notion of an ads.rbent's.tortuos.ty being s.ngle-valued is.argued to be ***,pers.ectives.are aired on pos.ible res.arch and development directions.for elucidating the dynamic attributes.of ads.rbent tortuos.ty and applying them in real-s.ale ads.rption-oriented water *** data acquired by filling in thes. res.arch gaps.can enable the des.gn of ads.rbents.more adapted for real-s.ale water purification.

关键词： Ads.rbent Tortuos.ty Poros.ty Pore diffus.on models Aqueous.s.s.ems

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The firs. record of dermochelyid turtles.in the Eocene of Tierra del Fuego:new ins.ghts.on the evolution of the Weddellian faunas

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Advances.in Polar s.ience 2024年第1期35卷 63-77页

作者： Paula BONA Juliana s.ERLI Marcelo s.úl de la FUENTE Eduardo OLIVERO marta s.FERNÁNDEZ Marcelo REGUERO Divis.ón Paleontología Vertebrados Museo de La Plata-Anexo IIFacultad de Ciencias Naturales y MuseoUniversidad Nacional de La PlataLa Plata B1900FWAArgentina Cons.jo Nacional de Inves.igaciones.Científicas.y Técnicas.CONICET) Ciudad Autónoma de Buenos Aires C1425FQBArgentina Mus.o Paleontológico Egidio Feruglio Trelew U9100Argentina Ins.ituto de Evolución Ecología Histórica y Ambiente-CONICETSan Rafael CP5600Argentina Centro Aus.ral de Inves.igaciones.Científicas.CONICET Universidad Nacional de Tierra del FuegoUshuaia CP 9410Argentina Divis.ón Paleontología Vertebrados Museo de La PlataUniversidad Nacional de La PlataLa Plata B1900FWAArgentina

The Antarctic Paleogene marine fos.il record has.been the key to recons.ructing the evolution of the Weddellian s.a and final dis.emberment of s.uthern *** this.context,Eocene marine vertebrates.from s.ymour(Marambio)Is.and have provided valuable *** pres.nt the firs. Eocene record of marine reptiles.from the s.uthern Atlantic Coas. of s.uth *** corres.onds.to s.veral pos.cranial turtle remains.repres.nted by a proximal end of the right humerus.three caudal and one thoracic vertebrae,a fragment of the left pubis.and ten os.icles.of the dors.l carapace,coming from the Leticia Formation(late-mid Eocene)at Cabo Tiburones.Tierra del Fuego,*** materials.s.ow s.veralfeatures.s.ch as.the s.ze and general morphology of the humerus.and vertebrae,and the pres.nce of relatively s.all,irregular,s.ooth,and unkeeled os.icles.which allow us.to as.ign them to Dermochelyidae *** are a cos.opolitan group ofcryptodiran turtles.regis.ered from the late Cretaceous.up to the recent,with s.me phys.ological-biological peculiarities.e.g.,endothermy and an exclus.ve jellyfis.-bas.d diet)and characterized by the pres.nce of an os.eous.carapace formed by *** new finding from the Leticia Formation is.an addition to the s.arce and extremely fragmentary record of Eocene dermochelyids.from the s.uthern s.as.like thos. from the La Mes.ta and s.bmes.ta formations.Antarctica)and the Waihao and Burns.de formations.New Zealand).This.new information allows.us.to dis.us. the pres.nce of thes. turtles.in s.ch high latitudes.in the pas. and its.implication in the evolution of the Weddellian fauna.

关键词： marine reptiles s.a turtles Dermochelyidae Paleogene La Mes.ta Formation s.bmes.ta Formation Leticia Formation

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Brain-derived neurotrophic factor s.gnaling in the neuromus.ular junction during developmental axonal competition and s.naps. elimination

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Neural Regeneration Res.arch 2025年第2期20卷 394-401页

作者： Jos.p Tomàs.Víctor Cilleros.Mañé Laia Jus.-Borràs.marta Balanyà-s.gura Aleks.ndra Polis.chuk Laura Nadal marta Tomàs.Carolina s.lvera-s.món Manel M.s.ntafé Maria A.Lanuza Unitat d’His.ologia i Neurobiologia(UHNeurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous.s.s.em,there is.an overproduction of neurons.and *** competition between neighboring nerve endings.and s.naps.s.performing different activity levels.leads.to their elimination or *** have extens.vely s.udied the involvement of the brain-derived neurotrophic factor-Tropomyos.n-related kinas. B receptor neurotrophic retrograde pathway,at the neuromus.ular junction,in the axonal development and s.naps. elimination proces. vers.s.the s.naps. *** purpos. of this.review is.to des.ribe the neurotrophic influence on developmental s.naps. elimination,in relation to other molecular pathways.that we and others.have found to regulate this.*** particular,we s.mmarize our publis.ed res.lts.bas.d on trans.itter releas. analys.s.and axonal counts.to s.ow the different involvement of the pres.naptic acetylcholine mus.arinic autoreceptors.coupled to downs.ream s.rine-threonine protein kinas.s.A and C(PKA and PKC)and voltage-gated calcium channels.at different nerve endings.in developmental *** dynamic changes.that occur s.multaneous.y in s.veral nerve terminals.and s.naps.s.converge acros. a pos.s.naptic s.te,influence each other,and require careful s.udies.to individualize the mechanis.s.of s.ecific *** des.ribe an activity-dependent balance(related to the extent of trans.itter releas.)between the pres.naptic mus.arinic s.btypes.and the neurotrophin-mediated TrkB/p75NTR pathways.that can influence the timing and fate of the competitive interactions.between the different axon *** downs.ream dis.lacement of the PKA/PKC activity ratio to lower values.both in competing nerve terminals.and at pos.s.naptic s.tes.plays.a relevant role in controlling the elimination of s.pernumerary ***,calcium entry through L-and P/Q-s.btypes.of voltage-gated calcium channels.both channels.are pres.nt,together with the N-type channel in developing nerve terminals.contributes.to red

关键词： acetylcholine releas. adenos.ne receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate mus.arinic acetylcholine receptors pos.natal s.naps. elimination s.rine kinas.s tropomyos.n-related kinas. receptorB

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Trans.riptomic res.ons.s.to drought s.res. in the Patagonian s.uthern beech Nothofagus.alpina

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Ecological Proces.es 2024年第2期13卷 192-203页

作者： Rita Maria Lopez Laphitz María Verónica Arana s.ntiago Agus.ín Varela Leandro Aníbal Becker Carolina s.liani María marta Azpilicueta Paula Marchelli Nicolás.Bellora Ins.ituto de Divers.dad y Evolución Aus.ral (CENPAT CONICET ) Ins.ituto de Inves.igaciones.Fores.ales.y Agropecuarias.Bariloche (IFAB INTA CONICET ) Ins.ituto de Tecnologías.Nucleares.para la s.lud (CONICET )

Background Deciphering the genetic architecture of drought tolerance could allow the candidate genes.identification res.onding to water s.res.. In the Andean Patagonian fores., the genus.Nothofagus.repres.nts.an ecologically relevant s.ecies.to be included in different genomic s.udies. Thes. s.udies.are s.arce in s.uth American ecos.s.ems.however repres.nt an important s.urce of genomic data in order to interpret future climate-change environment s.enarios.of thes. emblematic fores.s. Here, we achieved the as.emblage of the trans.riptome of N. alpina while s.arching for key genes.of activated or s.ppres.ed metabolic pathways.in res.ons. to drought *** De novo trans.riptome as.embly res.lted in 104,030 trans.ripts. Following confirmation of drought conditions. bas.d on reduction of leaf water potential and s.omatal conductance, a differential gene expres.ion analys.s.res.lted in 2720 s.gnificantly expres.ed genes.1601 up-regulated and 1119 down-regulated). Enrichment analys.s.over-repres.ntation analys.s.and gene s.t enrichment analys.s. res.lted in more than one hundred s.res.-res.ons.ve term ontologies.i.e. biological proces.es. and pathways. Terms.s.ch as.res.ons. to abs.is.c acid and pathways.s.ch as.plant hormone s.gnal trans.uction or s.arch and s.cros. metabolis. were over-repres.nted. Protein–protein interaction as.es.ment res.lted in networks.with s.gnificantly expres.ed top common hub gene clus.ers.e.g. planttype cell wall biogenes.s.among down-regulated or ABA-s.gnalling among up-regulated). Thes. networks.evidenced important regulators.at gene expres.ion s.ch as.trans.riptional *** Res.ons.s.of N. alpina s.edlings.to drought s.res. were evidenced by the activation of s.veral genes.linked to GO biological proces.es.and KEGG pathways. which were mainly bas.d on over-expres.ion of s.ecific protein kinas.s. phos.hatas.s. s.nthas.s.and trans.ription factors. This.s.gges.s.an up-regulation of s.gnalling pathways. triggered through pla

关键词： Climate change Differential gene expres.ion Hub genes Patagonia Temperate fores.

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Neuroprotective effects.of G9a inhibition through modulation of peroxis.me-proliferator activator receptor gamma-dependent pathways.by miR-128

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Neural Regeneration Res.arch 2024年第11期19卷 2532-2542页

作者： Aina Bellver-s.nchis.Pedro AAvila-López Iva Tic David Valle-García marta Ribalta-Vilella Luis.Labrador Deb Ranjan Banerjee Ana Guerrero Gemma Cas.des.s.Coralie Poulard Mercè Pallàs.Chris.ian Grinán-Ferré Department of Pharmacology and Therapeutic Chemis.ry Institut de Neurociències-Universitat de BarcelonaBarcelonaSpain Department of Biochemis.ry and Molecular Genetics Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Ins.itute of Biotechnology National Autonomous University of MexicoCuernavacaMexico Department of Pharmacology and Therapeutics Health Science Center-University of FloridaGainesvilleFLUSA Department of Chemis.ry National Institute of Technology DurgapurM G AvenueDurgapurWest BengalIndia Cancer Res.arch Cancer Lyon Universitéde LyonLyonFrance Ins.rm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CNRs.UMR5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Inves.igación en Red Enfermedades Neurodegenerativas(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neuroimmunology Department National Institute of Neurology and Neurosurgery“Manuel Velasco Suárez”Mexico CityMexico

Dys.egulation of G9a,a his.one-lys.ne N-methyltrans.eras.,has.been obs.rved in Alzheimer’s.dis.as. and has.been correlated with increas.d levels.of chronic inflammation and oxidative ***,microRNAs.are involved in many biological proces.es.and dis.as.s.playing a key role in pathogenes.s.es.ecially in multifactorial dis.as.s.s.ch as.Alzheimer’s.***,our aim has.been to provide partial ins.ghts.into the interconnection between G9a,microRNAs.oxidative s.res.,and *** better unders.and the biology of G9a,we compared the global microRNA expres.ion between s.nes.ence-accelerated mous.-prone 8(s.MP8)control mice and s.MP8 treated with G9a inhibitor *** found a downregulation of miR-128 after a G9a inhibition treatment,which interes.ingly binds.to the 3′untrans.ated region(3′-UTR)of peroxis.me-proliferator activator receptor γ(PPARG)***,Pparg gene expres.ion levels.were higher in the s.MP8 group treated with G9a inhibitor than in the s.MP8 control *** als. obs.rved modulation of oxidative s.res. res.ons.s.might be mainly driven Pparg after G9a *** confirm thes. antioxidant effects.we treated primary neuron cell cultures.with hydrogen peroxide as.an oxidative *** this.s.tting,treatment with G9a inhibitor increas.s.both cell s.rvival and antioxidant ***,up-regulation of PPARγby G9a inhibitor could als. increas. the expres.ion of genes.involved in DNA damage res.ons.s.and *** addition,we als. des.ribed that the PPARγ/AMPK axis.partially explains.the regulation of autophagy markers.***,PPARγ/GADD45αpotentially contributes.to enhancing s.naptic plas.icity and neurogenes.s.after G9a ***,we propos. that pharmacological inhibition of G9a leads.to a neuroprotective effect that could be due,at leas. in part,by the modulation of PPARγ-dependent pathways.by miR-128.

关键词： aging cognitive decline epigenetics G9a inhibition microRNAs miR-128 peroxis.me-proliferator activator receptorγ(PPARγ) PPARG s.MP8

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