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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)

Neurogenesis dynamics in the olfactory bulb:deciphering circuitry organization, function, and adaptive plasticity

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Neural regeneration research 2025年第6期20卷 1565-1581页

作者： moawiah m.Naffaa Department of Psychology and Neuroscience Duke UniversityDurhamNCUSA Department of Cell Biology Duke University School of MedicineDurhamNCUSA

Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased

关键词： network adaptability neurogenesis neuronal communication olfactory bulb olfactory learning olfactory memory synaptic plasticity

mitochondria–cGAS–STING axis is a potential therapeutic target for senescence-dependent inflammaging-associated neurodegeneration

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Neural regeneration research 2025年第3期20卷 805-807页

作者： Josém.Izquierdo Centro de Biología molecular Severo Ochoa(CBm) Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid(CSIC-UAM)MadridSpain

The word “senescence” comes from the Latin senescens, meaning “to begin to age”, and is characterized by a long-lasting but reversible block in proliferation, resulting from stress-induced cell cycle arrest of pre... 详细信息

关键词： Latin potential lasting

Brain-penetrating neurotrophic factor mimetics: HeR-096 as a disease-modifying therapy for Parkinson’s disease

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Neural regeneration research 2025年第4期20卷 1094-1095页

作者： Natalia Kulesskaya Kira m.Holmström Henri J.Huttunen Herantis Pharma Plc EspooFinland

Neurotrophic factors as a therapeutic approach in neurodegenerative diseases:A major unmet need in the field of central nervous system diseases is disease-modifying *** for decades there have been various symptomatic treatments available to alleviate the symptoms of the disease,disease-modification,*** that stop,significantly delay,or reverse the progression of the disease,has been turned out to a difficult goal to achieve.

关键词： diseases treatment therapeutic

A Generalized Array Factor for Time-modulated Hexagonal Based Antenna Array Geometry With Novel Trapezoidal Switching

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Ieee/CAA Journal of Automatica Sinica 2024年第9期11卷 1967-1972页

作者： Gopi ram Department of electronics and Communication engineering National Institute of TechnologyWarangal 506004India

The concept of the time-modulated array has been emerging as an alternative to the complex phase shifters,which lowers the cost of the array feeding network due to the utilization of radio frequency(RF)*** various forms of hexagonal antenna array geometries can be used for applications like surveillance tracking in phased array radar and wireless communication *** work proposes the generalized array factor(AF)for the hexagonal antenna array geometry based on time *** time modulation in generalized hexagonal geometry can maintain the fixed static amplitude excitation,giving more flexibility over ***,a novel trapezoidal switching function is also proposed and applied to the generalized array factor to enable future researchers to use this array factor in the field of advancement to observe how switching schemes like trapezoidal and rectangular affect the array pattern's side lobe level(SLL).The generalized equation can be utilized for the analysis and synthesis of radiation characteristics of the time-modulated hexagonal array(TmHA),time-modulated concentric hexagonal array(TmCHA),time-modulated hexagonal cylindrical array(TmHCA),and time-modulated hexagonal concentric cylindrical array(TmHCCA).The numerical result illustrates the generation of AF of time-modulated hexagonal structures and also shows that the trapezoidal switching sequence outperforms the rectangular switch using the cat swarm optimization(CSO)approach.

关键词： Hexagonal array geometry radiation pattern time-modulation trapezoidal pulse

Critical state model for structured soil

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Journal of Rock mechanics and Geotechnical engineering 2020年第3期12卷 630-641页

作者： Cristhian mendoza marcio muniz de Farias Department of Civil engineering Universidad Nacional de Colombia Sede ManizalesManizalesColombia Department of Civil and environmental engineering University of BrasiliaBrasiliaDFBrazil

Structure is an evident determinant for macroscopic behaviors of ***,this is not taken into account in most constitutive models,as structure is a rather complex issue in *** this,it is important to develop and implement simple models that can reflect this important aspect of soil *** paper tried to model structured soils based on well-established concepts,such as critical state and *** state is the core of the classic Cam Clay *** sub-loading concept implies adoption of an inner(sub-loading)yield surface,according to specific hardening rules for some internal strain-like state *** and co-workers proposed such internal variables for controlling density(p)and structure(ω),using a modified stress space,called ***,similar variables are used in the context of the better-known invariants(p and q)of the Cam Clay *** change requires explicit adoption of a non-associated flow rule for the sub-loading *** is accomplished by modifying the dilatancy ratio of the Cam Clay model,as a function of the new internal *** modifications are described and implemented under three-dimensional(3D)*** model is then applied to simulating laboratory tests under different stress paths and the results are compared to experiments reported for different types of structured *** good agreements show the capacity and potential of the proposed model.

关键词： elastoplasticity Cam clay with sub-loading Structured soil Tropical soil Non-associated flow rule

Characterizing drought in California:new drought indices and scenario-testing in support of resource management

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ecological Processes 2018年第1期7卷 1-13页

作者： Lorraine e.Flint Alan L.Flint John mendoza Julie Kalansky F.m.Ralph U.S.Geological Survey 6000 J.StSacramentoCA 95819USA Sonoma County Water Agency 404 Aviation Dr.Santa RosaCA 95403USA Scripps Institution of Oceanography 9500 Gilman Dr.La JollaCA 92093USA

Introduction:California’s recent drought(2012–2016)has implications throughout the state for natural resource management and adaptation planning and has generated many discussions about drought characterization and *** study characterizes drought conditions with two indices describing deficits in natural water supply and increases in landscape stress developed on the basis of water balance modeling,at a fine spatial scale to assess the variation in conditions across the entire state,and provides an in-depth evaluation for the Russian River basin in northern California to address local resource management by developing extreme drought scenarios for consideration in planning and ***:We employed the USGS Basin Characterization model to characterize drought on the basis of water supply(a measure of recharge plus runoff)and landscape stress(climatic water deficit).These were applied to the state and to the Russian River basin where antecedent soil moisture conditions were evaluated and extreme drought scenarios were developed and run through a water management and reservoir operations model to further explore impacts on water ***:Drought indices indicated that as of the end of water year 2016 when reservoirs were full,additional water supply and landscape replenishment of up to three average years of precipitation in some locations was needed to return to normal *** soil conditions in the Russian River were determined to contribute to very different water supply results for different years and were necessary to understand to anticipate proper watershed response to *** drought scenarios manifested very different kinds of drought and recovery and characterization helps to guide the management response to ***:These scenarios and indices illustrate how droughts differ with regard to water supply and landscape stress and how long warm droughts recover much more slowly than short very dry dro

关键词： California drought Russian River Water supply Basin Characterization model

Search for microglia-specific peptides:advances in the discovery toolbox

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Neural regeneration research 2025年第2期20卷 471-472页

作者： Ivan Sarabia Kyle m.Koss Department of Surgery University of ArizonaTucsonAZUSA

Uncontrolled and chronic inflammatory states in the central nervous system(CNS)are the hallmark of neurodegenerative pathology and every injury or stroke-related *** key mediators of these neuroinflammatory states are glial cells known as microglia,the resident immune cell at the core of the inflammatory event,and astroglia,which encapsulate inflammatory insults in proteoglycan-rich scar *** gliotic scar blocks significant portions of healthy axonal networking,preventing *** most neuroinflammation is exclusively based on the responses of said microglia,their phenotypes are suggested to follow those of macrophages;m1 and m2 are opposites of pro-and ***,microglial phenotypes have been identified to be on an inflammatory spectrum encompassing developmental,homeostatic,and reparative behaviors as opposed to their ability to affect devastating cell death cascades and scar tissue formation.

关键词： inflammation pathology death

SBL-JP-0004: A promising dual inhibitor of JAK2 and PI3KCD against gastric cancer

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Oncology research 2025年第1期33卷 235-243页

作者： Hassan m Otifi Department of Pathology College of Medicine King Khalid University Abha 62521 Saudi Arabia.

Background:Gastric cancer (GC) remains a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional therapies. The phosphoinositide 3-kinase and PI3K and Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathways play pivotal roles in GC progression, making them attractive targets for therapeutic interventions.methods:This study applied a computational and molecular dynamics simulation approach to identify and characterize SBL-JP-0004 as a potential dual inhibitor of JAK2 and PI3KCD kinases. KATOIII and SNU-5 GC cells were used for evaluation.results:SBL-JP-0004 exhibited a robust binding affinity for JAK2 and PI3KCD kinases, as evidenced by molecular docking scores and molecular dynamics simulations. Binding interactions and Gibbs binding free energy estimates confirmed stable and favorable interactions with target proteins. SBL-JP-0004 displayed an half-maximal inhibitory concentration (IC) value of 118.9 nm against JAK2 kinase and 200.9 nm against PI3KCD enzymes. SBL-JP-0004 exhibited potent inhibition of cell proliferation in KATOIII and SNU-5 cells, with half-maximal growth inhibitory concentration (GI) values of 250.8 and 516.3 nm, respectively. A significant elevation in the early phase apoptosis (28.53% in KATOIII cells and 26.85% in SNU-5 cells) and late phase apoptosis (17.37% in KATOIII cells and 10.05% in SNU-5 cells) were observed with SBL-JP-0004 treatment compared to 2.1% and 2.83% in their respective controls.Conclusion:The results highlight SBL-JP-0004 as a promising dual inhibitor targeting JAK2 and PI3KCD kinases for treating GC and warrant further preclinical and clinical investigations to validate its utility in clinical settings.

关键词： Dual inhibition Gastric cancer (GC) JAK2 molecular docking molecular dynamics simulation PI3KCD SBL-JP-0004