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Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón Pérez-núñez mar.a Fernanda González ana mar.a Avalos Lisette leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and notch/PI3K/AKT *** targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

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Effect of lepidium meyenii(maca)roots on spermatogenesis of male rats

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Asian Journal of Andrology 2001年第3期3卷 231-233页

作者： Gustavo F.Gonzales ana ruiz Carla Gonzales león Villegas Amanda Cordova Department of Physiological Sciences Faculty of Sciences and Philosophy and Instituto de Investigaciones de la Altura.Universidad Peruana Cayetano Heredia.Postal Office 1843.LimaPeru

Aim:To determine the effect of oral administration of an aqueous extract from the roots of lepidium meyenii(maca)on spermatogenesis in adult male ***;Male rats received an aqueous extract of the root(66.7 mg in onemL)twice a day for 14 consecutive ***:Treatment with lepidium meyenii resulted in an increase in theweights of testis and epididymis but not the seminal vesicle *** length and frequency of stages IX-XIV seminif-erous tubules,where mitosis occurred,were increased and stages I-VI were reduced in rats treated with ***;The lepidium meyenii root invigorates spermatogenesis in male rats by acting on its initialstages(IX-XIV).

关键词： spermatogenesis lepidium meyenii maca transillumination

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The Convex-Set Algebra and Intersection Theory on the Toric Riemann–Zariski Space

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Acta Mathematica Sinica,English Series 2022年第3期38卷 465-486页

作者： ana mar.a BOTERO Institut Für Mathematik Universität RegensburgUniversitätsstr.3193053RegensbergGermany

In previous work of the author,a top intersection product of toric b-divisors on a smooth complete toric variety is *** is shown that a nef toric b-divisor corresponds to a convex set and that its top inetersection number equals the volume of this convex *** goal of this article is to extend this result and define an intersection product of sufficiently positive toric b-classes of arbitrary *** this,we extend the polytope algebra of McMullen to the so called convex-set algebra and we show that it embeds in the toric b-Chow *** this way,the convex-set algebra can be viewed as a ring for an intersection theory for sufficiently positive toric *** an application,we show that some Hodge type inequalities are satisfied for the convex set algebra.

关键词： Convex geometry intersection theory toric varieties b-Chow groups Riemann–Zariski spaces

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Beacon-less Geographic Routing in Real Wireless Sensor networks

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Journal of Computer Science & Technology 2008年第3期23卷 438-450页

作者： Juan A.Sánchez Rafael marín-Pérez Pedro M.ruiz Department of Information and Communications Engineering University of MurciaSpain

Geographic Routing （GR） algorithms require nodes to periodically transmit HELLO messages to allow neighbors to know their positions （beaconing mechanism）. Beacon-less routing algorithms have recently been proposed to reduce the control overheads due to these messages. However, existing beacon-less algorithms have not considered realistic physical layers. Therefore, those algorithms cannot work properly in realistic scenarios. In this paper we present a new beacon-less routing protocol called BOSS. Its design is based on the conclusions of our open-field experiments using Tmote-sky sensors. BOSS is adapted to error-prone networks and incorporates a new mechanism to reduce collisions and duplicate messages produced during the selection of the next forwarder node. We compare BOSS with Beacon-less Routing （BLR） and Contention-Based Forwarding （CBF） algorithms through extensive simulations. The results show that our scheme is able to *** almost perfect packet delivery ratio （like BLR） while having a low bandwidth consumption （even lower than CBF）. Additionally, we carried out an empirical evaluation in a real testbed that shows the correctness of our simulation results.

关键词： geographic routing beacon-less forwarding performance evaluation real deployment

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Angle-to-angle and spur-to-spur distance analysis with high-resolution optical coherence tomography

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Eye and Vision 2020年第1期7卷 399-411页

作者： Robert Montés-Micó Pedro Tañá-Rivero Salvador Aguilar-Córcoles mar.a ruiz-Santos mar.a Dolores Rodríguez-Carrillo Ramón ruiz-Mesa Oftalvist Alicante and Jerez de la FronteraAlicanteSpain University of Valencia ValenciaSpain

Background:To measure angle-to-angle(ATA)and spur-to-spur(STS)distances along six meridians using highresolution swept-source optical coherence tomography(SS-OCT)and to compare those values with horizontal white-to-white(WTW)***:68 eyes from 68 patients were quantitatively assessed with the Anterion SS-OCT(Heidelberg Engineering,Heidelberg,Germany).ATA and STS distances were measured with the SS-OCT’s B-Scan in six cross-sectional images corresponding to the vertical(6-12 o’clock),1-7 o’clock,2-8 o’clock,horizontal(3-9 o’clock),4-10 o’clock and 5-11 o’clock *** was measured horizontally with the device’s infrared camera.A Pearson correlation analysis was carried out to compare ATA and STS distances with ***:The largest values were found for the vertical meridian and the shortest for the 2-8 o’clock meridian,both for ATA and STS *** statistically significant differences were found between WTW,ATA and STS along the horizontal meridian(p>0.1).However,ATA and STS showed statistically significant differences elsewhere,except for the horizontal and the 2-8 o’clock meridians(p>0.05).Moreover,we found that ATA and STS varied significantly depending on the meridian being assessed,except for ATA at 4-10 versus 3-9 o’clock and for STS at 4-10 versus 3-9 o’clock and at 3-9 versus 2-8 o’clock(p>0.1).R^(2) values ranged from 0.49 to 0.75 for ATA and STS at the different meridians,showing the best correlation at 3-9 o’clock meridian(0.64 and 0.75,respectively)and the worst at 6-12 o’clock meridian(R^(2)=0.49 for both ATA and STS).Conclusions:ATA and STS distances vary radially,thus showing that the anterior chamber is vertically ***,it is advisable to measure these two distances along the meridian to be used.

关键词： Angle-to-angle Spur-to-spur White-to-white Optical coherence tomography Swept-source Fourier domain

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Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso Josémartínez-Hernández Alejandro martín-Belmonte Rocío Alfaro-ruiz Miriam Fernández ana Esther Moreno-martínez mar Cuadrado-Tejedor ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic ***,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

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Inflammatory status in human hepatic cirrhosis

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World Journal of Gastroenterology 2015年第41期21卷 11522-11541页

作者： mar.a martínez-Esparza mar.a Tristán-Manzano Antonio J ruiz-Alcaraz Pilar García-Penarrubia Departamento de Bioquímica Biología Molecular (B) e Inmunología Facultad de Medicina IMIB Regional Campus of International Excellence "Campus Mare Nostrum" Universidad de Murcia

This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus(HCV) infection and chronic alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcoholinduced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis(HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared withHCV-related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to counter

关键词： Inflammation Macrophages Cirrhosis Alcohol Hepatitis C virus Cytokines Liver

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Allicin neuroprotective effect during oxidative/inflammatory injury involves AT1-Hsp70-inOS counterbalance axis

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BIOCELL 2020年第4期44卷 671-681页

作者： LUCIana MAZZEI mar.a BELÉn ruiz-ROSO nATALIA DE LAS HERAS SAnDRA BALleSTEROS CAROLInA TORRESPALAZZOLO leÓn FERDER AleJAnDRA BEATRIZ CAmarGO WALTER MAnUCHA Instituto de Medicina y Biología Experimental de Cuyo(IMBECU) Consejo Nacional de Investigaciones Científicas y Tecnológicas(CONICET)Mendoza5500Argentina Área de Farmacología Departamento de PatologíaFacultad de Ciencias MédicasUniversidad Nacional de Cuyo Centro UniversitarioMendoza5500Argentina Departamento de Fisiología Facultad de MedicinaUniversidad ComplutenseMadrid34523España IBAM Universidad Nacional de CuyoCONICETFacultad de Ciencias AgrariasMendozaM5528AHBArgentina Department of Pediatrics Nephrology DivisionMiller School of MedicineUniversity of MiamiMiami33012USA

The ancestral cultures have described many therapeutic properties of garlic,therefore,it is of central interest to elucidate the molecular basis explaining this millenary empirical ***,it has been demonstrated a neuroprotective effect of allicin–a phytochemical present in garlic-linked to oxidative-inflammatory *** improved neuronal injury by heat shock protein 70(Hsp70)and inducible nitric oxide synthase(inOS)***,allicin exerts renal protection involving a possible angiotensin type 1 receptor(AT1)*** connection,AT1 overexpression has been recognized as a central deleterious factor in many brain ***,there are no studies that evaluate AT1-Hsp70-inOS interaction as a mechanism linked to ***,our central aim is to evaluate if the allicin protective effect is associated with an AT1-Hsp70-inOS counterbalance *** this study,a murine microglial cell line(BV-2)was injured with lipopolysaccharides and treated or not with ***,it was evaluated cell viability,proinflammatory cytokine levels,cellular oxidative stress,inOS,Hsp70,and AT1 protein expression(cellular and mitochondrial fractions),nitrite levels,and protein-protein *** results demonstrated that allicin could prevent neuronal injury due to a reduction in oxidative stress and inflammatory status mediated by an AT1-Hsp70-inOS counterbalance axis linked to direct protein-protein interaction.

关键词： Allicin neuroinflammation BV-2 cells AT1 receptors inOS Hsp70

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Abscisic acid, a promising therapeutic molecule to prevent Alzheimer’s and neurodegenerative diseases

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neural Regeneration Research 2020年第6期15卷 1035-1036页

作者： ana mar.a Sánchez-Pérez Department of Medicine Universitat Jaume I

neuroinflammatory processes induce neuronal damage and underlie the onset of neurodegenerative pathologies,including Alzheimer’s disease(AD)(Calsolaro and Edison,2016).Several conditions,ranging from emotional stress to metabolic syndrome,including traumatic brain injury,chronic infections or gut microbiota disruption can cause or aggravate ***,aging is the major factor associated with neurodegenerative diseases.

关键词： degenerative Alzheimer diseases

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Long-term open circuit microbial electrosynthesis system promotes methanogenesis

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Journal of Energy Chemistry 2020年第2期29卷 3-6页

作者： Raúl Mateos Adrián Escapa mar.a Isabel San-martín Heleen De Wever ana Sotres Deepak Pant Chemical and Environmental Bioprocess Engineering Group Natural Resources Institute(IRENA)University of LeonLeon 24071Spain Department of Electrical Engineering and Automatic Systems Universidad de LeonLeon 24071Spain Reparation and Conversion Technology Flemish Institute for Technological Research(VITO)Mol 2400Belgium

Microbial electrosynthesis(MES) can potentially provide a mean for storing renewable energy surpluses as chemical energy. However, the fluctuating nature of these energy sources may represent a threat to MES, as the microbial communities that develop on the biocathode rely on the continuous existence of a polarized electrode. This work assesses how MES performance, product generation and microbial community evolution are affected by a long-period(6 weeks) power off(open circuit). Acetogenic and H2-producing bacteria activity recovered after reconnection. However, few days later syntrophic acetate oxidation bacteria and H2-consuming methanogens became dominant, producing CH4 as the main product, via electromethanogenesis and the syntrophic interaction between eubacterial and archaeal communities which consume both the acetic acid and the hydrogen present in the cathode environment. Thus,the system proved to be resilient to a long-term power interruption in terms of electroactivity. At the same time, these results demonstrated that the system could be extensively affected in both end product generation and microbial communities.

关键词： Biocathode Electromethanogenesis Microbial electrosynthesis Microbial community dynamics Methanogens Acetogens

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