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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 María Fernanda González Ana María 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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Noise-induced hippocampal damage:potential mechanisms

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Neural Regeneration Research 2022年第3期17卷 563-564页

作者： Sonia Jazmín Molina Laura Ruth Guelman Universidad de Buenos Aires Consejo Nacional de Investigaciones Científicas y TécnicasCentro de Estudios Farmacológicos y Botánicos(CEFyBOUBA-CONICET)Facultad de MedicinaBuenos AiresArgentina Universidad de Buenos Aires Facultad de Medicina1^(a) Cátedra de FarmacologíaBuenos AiresArgentina

Exposure to noise of high intensities(> 80 dB) is considered a stressful event and might produce both auditory and extra-auditory damage,including different central nervous system(CNS) *** the CNS,the hippocampus(HC),a structure related to several cognitive functions,has shown to be particularly susceptible to the effects of noise.

关键词： damage auditory injuries

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Role of platelets and breast cancer stem cells in metastasis

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World Journal of Stem Cells 2020年第11期12卷 1237-1254页

作者： Gretel Mendoza-Almanza Luis Burciaga-Hernandez Vilma Maldonado Jorge Melendez-Zajgla Jorge Olmos CONACYT Universidad Autónoma de Zacatecas.Zacatecas 98060Mexico Maestría en Ciencias Biomédicas Universidad Autónoma de ZacatecasZacatecas 98160Mexico Laboratorio de Epigenética Instituto Nacional de Medicina GenómicaCiudad de México 14610Mexico Génómica funcional del cáncer Instituto Nacional de Medicina GenómicaCiudad de México 14610Mexico Biotecnología Marina Centro de Investigación Científica y de Estudios Superiores de EnsenadaEnsenada 22860Mexico

The high mortality rate of breast cancer is mainly caused by the metastatic ability of cancer cells,resistance to chemotherapy and radiotherapy,and tumor regression *** recent years,it has been shown that the presence of breast cancer stem cells is closely associated with the migration and metastatic ability of cancer cells,as well as with their resistance to chemotherapy and *** tumor microenvironment is one of the main molecular factors involved in cancer and metastatic processes development,in this sense it is interesting to study the role of platelets,one of the main communicator cells in the human body which are activated by the signals they receive from the microenvironment and can generate more than one *** can ingest and release RNA,proteins,cytokines and growth *** the platelets interact with the tumor microenvironment,they are called"tumor-educated platelets."Tumor-educated platelets transport material from the tumor microenvironment to sites adjacent to the tumor,thus helping to create microenvironments conducive for the development of primary and metastatic *** has been observed that the clone capable of carrying out the metastatic process is a cancer cell with stem cell *** stem cells go through a series of processes,including epithelial-mesenchymal transition,intravasation into blood vessels,movement through blood vessels,extravasation at the site of the establishment of a metastatic focus,and site ***-educated platelets support all these processes.

关键词： Breast cancer stem cells Platelets Metastasis Tumor microenvironment Epithelial-mesenchymal transition

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Progesterone for the treatment of central nervous system disorders: the many signaling roads for a single molecule

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Neural Regeneration Research 2020年第10期15卷 1846-1847页

作者： Susana Laura González Universidad de Buenos Aires Facultad de Medicina Departamento de Bioquímica Humana Buenos Aires Laboratorio de Nocicepción y Dolor Neuropático Instituto de Biología y Medicina Experimental

Central nervous system(CNS)injuries and neurodegenerative diseases show a broad spectrum of common pathophysiological processes,including oxidative stress,neuroinflammation,excitotoxicity,demyelination and neurotransmission *** the past decades,valuable experimental investigations have helped to clarify the role and timing of these multiple molecular and cellular mechanisms in each of these particular disorders,which usually overlap and critically contribute to long-term ***,up to now,no definite cures or effective disease-modifying therapies are available for any of these *** has led to an active search of novel therapeutic approaches,including the repositioning of existing drugs for new indications,as a valid approach to promptly move candidate molecules to clinical trials.

关键词： injuries disorders drugs

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Protein synthesis modulation as a therapeutic approach for amyotrophic lateral sclerosis and frontotemporal dementia

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Neural Regeneration Research 2022年第7期17卷 1423-1430页

作者： Santiago E.Charif M.Florencia Vassallu Lara Salvañal Lionel M.Igaz IFIBIO Houssay Grupo de Neurociencia de SistemasFacultad de MedicinaUniversidad de Buenos Aires-CONICETBuenos AiresArgentina

Protein synthesis is essential for cells to perform life metabolic *** alterations of protein content can lead to particular *** have an intrinsic array of mechanisms and pathways that are activated when protein misfolding,accumulation,aggregation or mislocalization *** of them(like the unfolded protein response)represent complex interactions between endoplasmic reticulum sensors and elongation factors that tend to increase expression of chaperone proteins and/or repress translation in order to restore protein homeostasis(also known as proteostasis).This is even more important in neurons,as they are very susceptible to harmful effects associated with protein overload and proteostatic mechanisms are less effective with *** neurodegenerative pathologies such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,amyotrophic lateral sclerosis and frontotemporal dementia exhibit a particular molecular signature of distinct,unbalanced protein *** amyotrophic lateral sclerosis and frontotemporal dementia,the majority of cases present intracellular inclusions of ubiquitinated transactive response DNA-binding protein of 43 kDa(TDP-43).TDP-43 is an RNA binding protein that participates in RNA metabolism,among other *** of TDP-43(*** and mislocalization)can dramatically affect neurons,and this has been linked to disease *** of amyotrophic lateral sclerosis/frontotemporal dementia TDP-43-related mutations in cellular and animal models has been shown to recapitulate key features of the amyotrophic lateral sclerosis/frontotemporal dementia disease *** variants can be causative of degeneration onset and *** neurodegenerative diseases(including amyotrophic lateral sclerosis and frontotemporal dementia)have no cure at the moment;however,modulating translation has recently emerged as an attractive approach that can be performed at several steps(***

关键词： amyotrophic lateral sclerosis frontotemporal dementia neurodegeneration neurodegenerative diseases protein imbalance protein synthesis modulation proteostasis therapeutical compounds transactive response DNA-binding protein of 43 kDa translation unfolded protein response

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Locomotor recovery after spinal cord injury:intimate dependence between axonal regeneration and re-connection

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Neural Regeneration Research 2022年第3期17卷 553-554页

作者： Hector Ramiro Quintá Consejo Nacional de Investigaciones científicas y Técnicas CONICET Laboratorio de medicina Experimental“Dr.Jorge E.Toblli” Hospital AlemánBuenos AiresArgentina

Traumatic spinal cord injuries(SCI) are characterized by damage in the integrity of the spinal cord,which results in either temporary or permanent alterations in the locomotor,sensory and/or autonomic functions(Yezierski,2009).The traumatic event leads to impairments in voluntary control of movement below the injury by affecting the connection between the brain and the neurons localized in the spinal cord.

关键词： injuries alterations damage

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The balance between efficient anti-inflammatory treatment and neuronal regeneration in the olfactory epithelium

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Neural Regeneration Research 2018年第10期13卷 1711-1714页

作者： Seo Young Chang Isaias Glezer department of Biochemistry Escola Paulista de MedicinaUniversidade Federal de SAo Paulo

The sense of smell is important for human quality of life. This sophisticated sensorial system relies on the detection of odorant molecules that engage receptors expressed in the cilia of dedicated neurons that constitute the olfactory epithelium（OE）. Importantly, the OE is a highly active site of adult neurogenesis where short-lived neurons are efficiently replenished, even after massive neuronal cell loss. It is suggested that the degree of olfactory function recovery after OE injury may depend on the nature of the lesion（traumatic, chemical, infectious or inflammatory）, as well on the velocity of cellular regeneration. Topical steroidal anti-inflammatory drugs, such as glucocorticoids, are routinely prescribed for treating upper airway inflammatory conditions, such as chronic rhinosinusitis. While the therapeutic strategy aims to minimize the inflammatory damage and dysfunction to nasal air conduction, new evidences raise concerns if such drugs may impair neuronal regeneration in the OE. In consequence, new directions are necessary in terms of drug development or prescription, in order to preserve olfactory function through lifelong repeated episodes of chronic inflammation in the upper respiratory tract. Here we discuss mechanisms involved in glucocorticoid deleterious effects to OE regeneration and possible therapeutic alternatives considering relevant side effects.

关键词： anti-inflammatory drugs corticosteroids hyposmia inflammation rhinosinusitis olfactory epithelium sensory neurons cell proliferation

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Meningeal T-cells in the cross-talk between memory consolidation and sleep

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Neural Regeneration Research 2023年第12期18卷 2687-2688页

作者： Rodrigo Pacheco Valentina Ugalde Laboratorio de Neuroinmunología Centro Científico y Tecnológico de Excelencia Ciencia&VidaFundación Ciencia&VidaSantiagoChile Facultad de medicina y Ciencia Universidad San SebastiánSantiagoChile

Some years ago,the infiltration of T-cells into the central nervous system(CNS) was considered a pathological condition ***,during the last two decades,a growing body of studies has shown that T-cells are essential pl... 详细信息

关键词： behavior. sleep consolidation

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Leishmaniasis in the Argentine Republic: Temporal and geographical distribution from 2013 to 2017

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Asian Pacific Journal of Tropical Medicine 2019年第7期12卷 300-305页

作者： GermanóMaría J Salomón María C Neira Gisela Lozano Esteban Mackern-Oberti Juan P Cargnelutti Diego E Consejo Nacional de Investigaciones científicas y Técnicas Centro Científico y Tecnológico de MendozaInstituto de Medicina y Biología Experimental de CuyoMendozaArgentina Universidad Nacional de Cuyo Facultad de Ciencias Médicasárea de ParasitologíaMendozaArgentina Universidad Juan Agustín Maza Facultad de Ciencias Veterinarias y AmbientalesCentro de Investigación en Parasitología RegionalMendozaArgentina Universidad Nacional de Cuyo Facultad de Ciencias MédicasInstituto de FisiologíaMendozaArgentina

Objective: To assess the temporal and geographical distribution of confirmed cases of cutaneous, mucocutaneous and visceral leishmaniasis in the Argentine Republic from 2013 to 2017. Methods: A retrospective study was carried out using data collected from the Integrated Surveillance Bulletin database of the National System of Health Surveillance. Confirmed cases of cutaneous, mucocutaneous and visceral leishmaniasis up to the 52 nd epidemiological week of each year was included. Results: In the 5 years period, 1 295 confirmed leishmaniasis cases were reported in the Argentine Republic. One thousand twenty-eight(1 028) cases corresponded to cutaneous leishmaniasis(87.10%), being the most common type of leishmaniasis. Mucocutaneous leishmaniasis was in the second place in the country with 115 cases reported, mostly in the Northwest and Northeast regions. A total of 52 individuals with visceral leishmaniasis were identified and Misiones Province was the most affected. Conclusions: It is important to analyze the temporal and geographical distribution of leishmaniasis in order to provide an adequate management and surveillance.

关键词： Leishmaniasis Epidemiology Argentine Republic Temporal distribution Geographical distribution

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Dietary carbohydrate-to-protein ratio influences growth performance,hepatic health and dynamic of gut microbiota in atlantic salmon(Salmo salar)

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Animal Nutrition 2022年第3期10卷 261-279页

作者： Alejandro Villasante Carolina Ramírez Hector Rodríguez Patricio Dantagnan Adrian Hernandez Elías Figueroa Jaime Romero Facultad de medicina Veterinaria y Agronomía Universidad de Las AmericasSantiagoChile Laboratorio de Biotecnología de Alimentos Unidad de AlimentosInstituto de Nutricion y Tecnología de Los Alimentos(INTA)Universidad de ChileSantiagoChile Programa de Anatomía y Biología del desarrollo Facultad de MedicinaUniversidad de ChileSantiagoChile Núcleo de Investigacion en Produccion Alimentaria Facultad de Recursos NaturalesUniversidad Catolica de TemucoTemucoChile

Atlantic salmon(Salmo salar)fed a carbohydrate-rich diet exhibit suboptimal growth performance,along with other metabolic *** is well known that gut microbes play a pivotal role in influencing metabolism of the host,and these microbes can be modified by the *** main goal of the present study was to determine the effect of feeding graded levels of digestible carbohydrates to Atlantic salmon on the distal intestine digesta microbiota at 3 sampling times(i.e.,weeks 4,8 and 12),during a 12-week trial.A low carbohydrate-to-high protein diet(LC/HP,0%wheat starch),a medium carbohydrate-tomedium protein diet(MC/MP,15%wheat starch)or a high carbohydrate-to-low protein diet(HC/LP,30%wheat starch)was fed to triplicate fish tanks(27 to 28 fish per tank).We performed an in-depth characterization of the distal intestine digesta ***,growth parameters,liver histology and the expression of genes involved in hepatic neolipogenesis in fish were *** fed a HC/LP diet showed greater hepatosomatic and viscerosomatic indexes(P=0.026 and P=0.018,respectively),lower final weight(P=0.005),weight gain(P=0.003),feed efficiency(P=0.033)and growth rate(P=0.003)compared with fish fed the LC/HP ***,feeding salmon a high digestible carbohydrate diet caused greater lipid vacuolization,steatosis index(P=0.007)and expression of fatty acid synthase(fas)and delta-6 fatty acyl desaturase(d6fad)(P=0.001 and P=0.001,respectively)in the liver compared with fish fed the LC/HP ***,the major impact of feeding a carbohydrate-rich diet to Atlantic salmon in beta diversity of distal intestine digesta microbiota was observed at week 4(HC/LP vs MC/MP and HC/LP vs LC/HP;P=0.007 and P=0.008,respectively)and week 8(HC/LP vs MC/MP;P=0.04),no differences between experimental groups were detected after 12 weeks of ***,at the end of the trial,there was a negative correlation between lactic acid bacteria(LAB)members,including Leuconostoc and Lactobacil

关键词： Microbiota Microbiome Atlantic salmon Steatosis Lactic acid bacteria Probiotics

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