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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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From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

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neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero Hospital nacional de parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Unit for neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoratio

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

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Data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

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neural Regeneration Research 2025年第7期20卷 1997-1998页

作者： paz Cartas-Cejudo Adriana Cortés Mercedes Lachén-Montes Elena Anaya-Cubero Joaquín Fernández-Irigoyen Enrique Santamaría Clinical neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous *** diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual *** the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining *** last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

关键词： diseases drug amyloid

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Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

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neural Regeneration Research 2025年第8期20卷 2395-2407页

作者： María norte-Muñoz María portela-Lomba paloma Sobrado-Calvo Diana Simón Johnny Di pierdomenico Alejandro Gallego-Ortega Mar pérez JoséMCabrera-Maqueda Javier Sierra Manuel Vidal-Sanz María Teresa Moreno-Flores Marta Agudo-Barriuso Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la SaludMurciaSpain Experimental Sciences Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain Anatomy Histology and Neuroscience DepartmentMedicine FacultyUniversidad Autónoma de MadridMadridSpain Center of neuroimmunology Service of NeurologyLaboratory of Advanced Imaging in Neuroimmunological DiseasesHospital Clínic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)and Universitat de BarcelonaBarcelonaSpain Medicine Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic ***,it is unknown whether olfactory ensheathing glia also have neuroprotective *** ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion ***,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve *** ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive *** and gene expression analyses were *** bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡ*** and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an *** axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 *** these retinas,microglial anatomical activation was higher than after optic nerve crush *** intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or ***,neuroprotection of axotomized retinal ganglion cells did not improve with these *** different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

关键词： cell therapy immune recognition major histocompatibility complex class II(MHCII) neuroprotection olfactory ensheathing glia retinal ganglion cells

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The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

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neural Regeneration Research 2025年第11期20卷 3317-3329页

作者： Jennifer M.Colón-Mercado Aranza I.Torrado-Tapias Iris K.Salgado Jose M.Santiago Samuel E.Ocasio Rivera Dina p.Bracho-Rincon Luis H.pagan Rivera Jorge D.Miranda Department of physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA national Institutes of Health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of puerto Rico Carolina CampusCarolinaPRUSA Institute of neurobiology San JuanPRUSA

In addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma

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passive technologies for future large-scale photonic integrated circuits on silicon: polarization handling, light non-reciprocity and loss reduction

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Light(Science & Applications) 2012年第1期1卷 134-145页

作者： Daoxin Dai Jared Bauters John E bowers Department of Electrical and Computer Engineering University of CaliforniaSanta BarbaraCA 93106USA Centre for Optical and Electromagnetic Research State Key Laboratory for Modern Optical InstrumentationZhejiang UniversityZijingangHangzhou 310058China

Silicon-based large-scale photonic integrated circuits are becoming important,due to the need for higher complexity and lower cost for optical transmitters,receivers and optical *** this paper,passive technologies for large-scale photonic integrated circuits are described,including polarization handling,light non-reciprocity and loss *** design rule for polarization beam splitters based on asymmetrical directional couplers is summarized and several novel designs for ultra-short polarization beam splitters are reviewed.A novel concept for realizing a polarization splitter–rotator is presented with a very simple fabrication *** of silicon-based light non-reciprocity devices(e.g.,optical isolator),which is very important for transmitters to avoid sensitivity to reflections,is also demonstrated with the help of magneto-optical material by the bonding ***-loss waveguides are another important technology for large-scale photonic integrated ***-low loss optical waveguides are achieved by designing a Si3n4 core with a very high aspect *** loss is reduced further to,0.1 dB m21 with an improved fabrication process incorporating a high-quality thermal oxide upper cladding by means of wafer *** the developed ultra-low loss Si3n4 optical waveguides,some devices are also demonstrated,including ultra-high-Q ring resonators,low-loss arrayed-waveguide grating(de)multiplexers,and high-extinction-ratio polarizers.

关键词： integration low loss non-reciprocal polarization silicon

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national trends in resection of the distal pancreas

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World Journal of Gastroenterology 2012年第32期18卷 4342-4349页

作者： Armando Rosales-Velderrain stev.n p bowers Ross F Goldberg Tatyan M Clarke Mauricia A Buchanan John A Stauffer Horacio J Asbun Department of General Surgery Mayo Clinic FloridaJacksonvilleFL 32225United States

AIM:To investigate national trends in distal pancreatectomy(Dp) through query of three national patient care ***:From the nationwide Inpatient Sample(nIS,2003-2009),the national Surgical Quality Improvement project(nSQIp,2005-2010),and the Surveillance Epidemiology and End Results(SEER,2003-2009) databases using appropriate diagnostic and procedural codes we identified all patients with a diagnosis of a benign or malignant lesion of the body and/or tail of the pancreas that had undergone a partial or distal *** of laparoscopy was defined in nIS by the International Classification of Diseases,ninth Revision correspondent procedure code;and in nSQIp by the exploratory laparoscopy or unlisted procedure current procedural terminology *** SEER,patients were identified by the International Classification of Diseases for Oncology,Third Edition diagnosis codes and the SEER program Code Manual,third edition procedure *** analyzed the databases with respect to trends of inpatient outcome metrics,oncologic outcomes,and hospital volumes in patients with lesions of the neck and body of the pancreas that underwent operative ***:nIS,nSQIp and SEER identified 4242,2681 and 11 082 Dp resections,***,laparoscopy was utilized in 15%(nIS) and 27%(nSQIp).no significant increase was seen over the course of the *** was performed for malignancy in 59%(nIS) and 66%(nSQIp).neither patient Body mass index nor comorbidities were associated with operative approach(p = 0.95 and p = 0.96,respectively).Mortality(3% vs 2%,p = 0.05) and reoperation(4% vs 4%,p = 1.0) was not different between laparoscopy and open *** complications(10% vs 15%,p pital costs [44 741 dollars,interquartile range(IQR) 28 347-74 114 dollars vs 49 792 dollars,IQR 13 299-73 463,p = 0.02] and hospital length of stay(7 d,IQR 4-11 d vs 7 d,IQR 6-10,p n laparoscopy was *** and two year sur

关键词： Laparoscopic distal pancreatectomy Trends nationwide Inpatient Sample national Surgical Quality Improvement project Surveillance epidemiology and end results

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FpGA Implementation of Deep Leaning Model for Video Analytics

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Computers, Materials & Continua 2022年第4期71卷 791-808页

作者： p.n.palanisamy n.Malmurugan Mahendra College of Engineering SalemIndia

In recent years,deep neural networks have become a fascinating and influential research subject,and they play a critical role in video processing and ***,video analytics are predominantly hardware centric,exploration of implementing the deep neural networks in the hardware needs its brighter light of ***,the computational complexity and resource constraints of deep neural networks are increasing exponentially by *** neural networks are one of the most popular deep learning architecture especially for image classification and video *** these algorithms need an efficient implement strategy for incorporating more real time computations in terms of handling the videos in the *** programmable Gate arrays(FpGA)is thought to be more advantageous in implementing the convolutional neural networks when compared to Graphics processing Unit(GpU)in terms of energy efficient and low computational *** still,an intelligent architecture is required for implementing the Cnn in FpGA for processing the *** paper introduces a modern high-performance,energy-efficient Bat pruned Ensembled Convolutional networks(BpEC-Cnn)for processing the video in the *** system integrates the Bat Evolutionary pruned layers for Cnn and implements the new shared Distributed Filtering Structures(DFS)for handing the filter layers in Cnn with pipelined data-path in *** addition,the proposed system adopts the hardware-software co-design methodology for an energy efficiency and less computational *** extensive experimentations are carried out using CASIA video datasets with ARTIX-7 FpGA boards(number)and various algorithms centric parameters such as accuracy,sensitivity,specificity and architecture centric parameters such as the power,area and throughput are *** results are then compared with the existing pruned Cnn architectures such as Cnn-prunner in which the proposed architecture has been shown

关键词： Deep neural networks field programmable gate arrays convolutional neural networks distributed filtering structures bat-pruned

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Spray Characteristics of Biodiesel Fuel in Constant Volume Chamber using Multi-response Optimization Technique

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Journal of Thermal Science 2016年第6期25卷 581-588页

作者： p.Raghu n.nallusamy Sri Venkateswara College of Engineering Department of Mechanical Engineering SSn College of Engineering Department of Mechanical Engineering

This study discusses about the optimization of spray characteristics of biodiesel fuel in a spray *** factors namely,fuel injection pressure,fuel temperature and fuel blends were chosen as the influencing factor for the set *** levels were chosen in each factor and spray tip penetration,spray cone angle and Sauter mean diameter(SMD) were taken as the response *** were designed by employing design of experiments method and Taguchi full factorial array was used to conduct the tests with different levels of the chosen *** Response Signal to noise ratio(MRSn) was calculated for the response variables and the optimum combination level of factors was obtained simultaneously using Taguchi's parametric *** experiments were conducted for the obtained optimum combination level of factors and the results were compared with the normal operating conditions and significant improvement were observed in the response variables.

关键词： spray penetration factorial weighting chosen conduct chamber parametric normalized blends

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Operating characteristics of a high radius pre-swirl cooling system

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航空动力学报 2007年第6期22卷 849-858页

作者： p.new p.R.n.Childs Rolls-Royce supported University Technology Centre in Aero-Thermal Systems University of SussexUK

An experimental investigation into pre-swirl effectiveness and receiver hole discharge coefficient characteristics for a high radius injection pre-swirl cooling systems was carried out on a physically representative experimental rig with a 450 mm diameter *** receiver holes and pre-swirl nozzle were located at a radius of 181 mm and 180 mm *** experimental work was mainly conducted at 5 000～12 000 r/min,4 bar absolute pressure and 1.132 kg/s air *** maximum air supply temperature was 190 ℃.pressure and temperature distributions in the pre-swirl system were examined with an emphasis on the velocity effectiveness of the pre-swirl system as a whole and on the discharge coefficients of the rotating 'receiver holes' in the *** results showed that the velocity effectiveness increased with increasing swirl ratio resulting in reduced blade cooling flow *** seal flow configurations caused very different effectiveness at different speeds,but outflow through the inner and outer seals always gave the highest effectiveness compared other *** the seal flow rate reduced the *** the coefficient of discharge,except for the low speed range,it increased with increase in swirl ratio for most speeds.

关键词：前漩涡冷却系统燃气涡轮速率流量系数

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