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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)

Efficacy of antimicrobials in preventing resistance in solid organ transplant recipients:A systematic review of clinical trials

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World Journal of Transplantation 2025年第1期15卷 156-164页

作者： Carlos M Ardila Pradeep K Yadalam Jaime ramírez-Arbelaez Department of Basic Sciences Faculty of Dentistry Biomedical Stomatology Research GroupUniversidad de Antioquia U de AMedellín 0057Colombia Department of Postdoctoral Program CIFE University CenterCuernavaca 62330MorelosMexico Department of Periodontics Saveetha Dental CollegeSaveetha Institute of Medical and HealthSIMATSSaveetha UniversityChennai 600077Tamil NaduIndia Department of Transplantation Hospital San Vicente FundaciónRionegro 054047Colombia

BACKGROUND In the absence of effective antimicrobials,transplant surgery is not viable,and antirejection immunosuppressants cannot be administered,as resistant infections compromise the life-saving goal of organ *** To evaluate the efficacy of antimicrobials in preventing resistance in solid organ transplant *** A systematic review was conducted using a search methodology consistent with the preferred reporting items for systematic reviews and *** review included randomized clinical trials that evaluated the efficacy of antimicrobial agents(prophylactic or therapeutic)aimed at preventing antimicrobial *** search strategy involved analyzing multiple databases,including PubMed/MEDLINE,Web of Science,Embase,Scopus,and SciELO,as well as examining gray literature sources on Google Scholar.A comprehensive electronic database search was conducted from the databases’inception until May 2024,with no language *** After the final phase of the eligibility assessment,this systematic review ultimate-ly included 7 articles.A total of 2318 patients were *** most studied microorganisms were cytomegalovirus,although vancomycinresistant enterococci,Clostridioides difficile,and multidrug-resistant Enterobacterales were also *** antimicrobials used in the interventions were mainly maribavir,valganciclovir,gancic-lovir,and *** concern,all clinical trials showed significant proportions of resistant microorga-nisms after the interventions,with no statistically significant differences between the groups(mean resistance 13.47%vs 14.39%),except for two studies that demonstrated greater efficacy of maribavir and valganciclovir(mean resistance 22.2%vs 41.1%in the control group;P<0.05).The total reported deaths in three clinical trials were 75,and there were 24 graft rejections in two *** All clinical trials reported significant proportions of antimicrobial-resistant microor

关键词： Antimicrobial resistance Antimicrobials Antivirals Solid organ transplant recipients Infections Microorganisms Cytomegalovirus

In silico analysis of lncRNA-miRNA-mRNA signatures related to Sorafenib effectiveness in liver cancer cells

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World Journal of Gastroenterology 2025年第3期31卷 84-102页

作者： Patricia de la.cruz-Ojeda Ester Parras-Martínez Raquel Rey-Pérez Jordi Muntané Functional Genomics of Solid Tumors Laboratory Centre de Recherche des CordeliersParis 75006France Department of Oncology Surgery Cell Therapy and Organ TransplantationInstitute of Biomedicine of SevilleVirgen del Rocio University HospitalSeville 41013Spain Biomedical Research Center for Hepatic and Digestive Diseases CIBERehdMadrid 28029Spain Department of Medical Physiology and Biophysics University of SevilleSeville 41009Spain

BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of primary liver cancer with varied incidence and epidemiology *** is still a recommended treatment for a large proportion of patients with advanced *** patterns of treatment responsiveness have been identified in differentiated hepatoblastoma HepG2 cells and metastatic HCC SNU449 *** To define the long non-codingRNA-microRNA-mRNA(lncRNA-miRNA-mRNA)predicted signatures related to selected hallmarks of cancer(apoptosis,autophagy,cell stress,cell dedifferentiation and invasiveness)in RNAseq studies using Sorafenib-treated HepG2 and SNU449 *** available software analyses allowed us to establish the lncRNA-miRNA-mRNA regulatory axes following treatment in HepG2 and SNU449 *** HepG2 and SNU449 cells were treated with Sorafenib(10μmol/L)for 24 *** RNA,including small and long RNA,was extracted with a commercial miRNeasy *** was carried out for the identification of changes in lncRNA-miRNA-mRNA regulatory *** MALAT,THAP9-AS1 and SNGH17 appeared to coordinately regulate miR-374b-3p and miR-769-5p that led to upregulation of SMAD7,TIRARP,TFAP4 and FAXDC2 in HepG2 ***12,EPB41 L4A-AS1,LINC01578,SNHG12 and GAS5 interacted with let-7b-3p,miR-195-5p and VEGFA in SNU449 *** axes MALAT1/hsamir-374b-3p/SMAD7 and MALAT1/hsa-mir-769-5p/TFAP4 were of high relevance for Sorafenib response in HepG2 cells,whereas PVT1/hsa-miR-195-5p/VEGFA was responsible for the differential response of SNU449 cells to Sorafenib *** Critical lncRNAs acting as sponges of miRNA were identified that regulated mRNA expression,whose proteins mainly increased the antitumor effectiveness of the treatment(SMAD7,TIRARP,TFAP4,FAXDC2 and ADRB2).However,the broad regulatory axis leading to increased VEGFA expression may be related to the side effect of Sorafenib in SNU449 cells.

关键词： Cell culture Hepatocellular carcinoma Non-coding RNA RNAseq Sorafenib

Does mesenchymal stem cell’s secretome affect spinal sensory circuits?Implication for pain therapies

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Neural Regeneration Research 2025年第1期20卷 181-183页

作者： Francesco Ferrini Esri H.Juárez Adalberto Merighi Department of Veterinary Sciences University of TurinGrugliascoTOItaly Department of Psychiatry and Neuroscience UniversitéLavalQuébec CityQCCanada

Mesenchymal stem cells(MSCs)are multipotent adult stem cells of mesodermal origin that can be isolated from various tissues,including bone marrow,tooth pulp,adipose tissue,and umbilical *** have gained significant attention in regenerative medicine due to their ability to modulate the immune system and favor tissue *** enrich the medium in which they are cultivated with a broad range of bioactive molecules,including growth factors,cytokines,chemokines,enzymes,nucleic acids,and extracellular vesicles that collectively compose the MSC *** increasing number of pre-clinical studies suggest that delivering in vivo an MSC-conditioned medium(i.e.,the medium collected from MSC cultures after at least 3 days of exposure)exerts neuroprotective and anti-inflammatory effects in a variety of neurological conditions.

关键词： protective clinical collective

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

Hydrogen production from dry reforming of methane,using CO_(2)previously chemisorbed in the Li_(6)Zn_(1-x)Ni_(x)O_(4)solid solution

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Journal of Environmental Sciences 2025年第3期149卷 535-550页

作者： Yocelin B.González-González Fernando Plascencia-Hernández Rubén Mendoza.cruz Heriberto Pfeiffer Instituto de Investigaciones en Materiales Universidad Nacional Autónoma de MéxicoCircuito exterior s/nCiudad UniversitariaDel.CoyoacánCP 04510CdMxMexico

Li_(6)ZnO_(4)was chemically modified by nickel addition,in order to develop different compositions of the solid solution Li_(6)Zn_(1-x)Ni_(x)O_(4).These materials were evaluated bifunctionally;analyzing their CO_(2)capture performances,aswell as on their catalytic properties for H_(2)production via dry reforming of methane(DRM).The crystal structures of Li_(6)Zn_(1-x)Ni_(x)O_(4)solid solution samples were determined through X-ray diffraction,which confirmed the integration of nickel ions up to a concentration around 20 mol%,meanwhile beyond this value,a secondary phase was *** results were supported by XPS and TEM ***,dynamic and isothermal thermogravimetric analyses of CO_(2)capture revealed that Li_(6)Zn_(1-x)Ni_(x)O_(4)solid solution samples exhibited good CO_(2)chemisorption efficiencies,similarly to the pristine Li_(6)ZnO_(4)chemisorption trends ***,a kinetic analysis of CO_(2)isothermal chemisorptions,using the Avrami-Erofeev model,evidenced an increment of the constant rates as a function of the Ni *** Ni^(2+)ions incorporation did not reduce the CO_(2)capture efficiency and kinetics,the catalytic properties of thesematerialswere evaluated in the DRM *** demonstrated that nickel ions favored hydrogen(H_(2))production over the pristine Li_(6)ZnO_(4)phase,despite a second H2 production reaction was determined,methane ***,Li_(6)Zn_(1-x)Ni_(x)O_(4)ceramics can be employed as bifunctional materials.

关键词： Dry reforming of methane(DRM) CO_(2)chemisorption H_(2)production Solid solution Li_(6)ZnO_(4)

Multiple Chemical Sensitivity: A Sickness of Suffering, Not of Dying. Descriptive Study of 33 Cases

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Health 2025年第1期17卷 65-81页

作者： Blanca Navas-Soler Aarón Gutiérrez-Pastor Antonio Palazón-Bru Jorge Vallejo-Ortega Álex Méndez-Jover Celia Santano-Pérez Carmen Seguí-Pérez Marc Seguí-Pérez Sonia Cascant-Pérez Juan Carlos López-Corbalán Míriam Pérez-Cardona ramón Pérez-Doménech Antonio Hernández-García Patricia Lorca-Amorrich Ana Belén Llinares-Llinares Cristina Valverde-Cámara Rosa María Bustos-Martínez Juan Manuel Núñez-cruz Isidro Hernández-Isasi José Juan Martínez-Pérez José Manuel Santano-López María Dolores Jover-Ríos Juan Méndez-Mora José Miguel Seguí-Ripoll Internal Medicine Service University Hospital of San Juan de Alicante Alicante Spain Family and Community Medicine Service University Hospital of San Juan de Alicante Alicante Spain Foundation for the Promotion of Health and Biomedical Research of the Valencian Community (FISABIO) University Hospital of San Juan de Alicante Alicante Spain Faculty of Physics University of Alicante Alicante Spain Department of Clinical Medicine Medical School University Miguel Hernandez de Elche Alicante Spain CEU Veterinary School University Cardenal Herrera Alfara del Patriarca Campus Valencia Spain Secondary School Marist Brothers High School Alicante Spain Primary Medicine Hospital Francesc Borgia of Gandia Valencia Spain Faculty of Medicine CEU Cardenal Herrera University Alfara del Patriarca Campus Valencia Spain Faculty of Economics University of Alicante Alicante Spain Department of Internal Medicine Hospital La Vega Baja of Orihuela Alicante Spain

Objective: We describe patients with MCS, the evolution of the Quick Environmental Exposure and Sensitivity Inventory (QEESI) score with a special focus on people whose fillings were removed. Methods: We have conducted a retrospective longitudinal cohort study in patients diagnosed with MCS and attended in the outpatient Internal Medicine department of the University Hospital of San Juan de Alicante, from January 1, 2008 to January 1, 2021. Sociodemographic, clinical, QEESI and treatment-related variables were collected. We performed descriptive and inferential analyses. Mixed linear models were used to analyze the QEESI. Calculations were carried out with an α error of 5%. Results: Thirty-three patients were included (72.7% women, mean age 56.2). MCS was mainly triggered by mercury (N = 20) and food intolerance (N = 22). The mean interval from symptoms onset was 120 months (SD 81.6). 114 QEESIs were analyzed: 82 (N = 17 without amalgams) and 32 (N = 16 with amalgams). In patients without amalgams, severity scores increased across all subscales except the masking index (vs. with amalgams). Mean scores for the group without amalgams (vs. with amalgams) were: chemical intolerance, 62.8 points (vs. 63.4 and 46.7);other intolerances, 52.7 points (vs. 62.8 and 50.3);symptom severity, 63.2 (vs. 76.7 and 63.3);masking index, 3.9 (vs. 3.2 and 2.8);and life impacts, 63.1 (vs. 58.4 and 49.8). Conclusion: The profile of patient with MCS is a middle-aged woman who is a frequent user of healthcare services, presents a long diagnostic delay and has borne a great personal, work and socioeconomic impact. The QEESI is useful for the clinical follow-up of patients, including the optimal treatment response in the case of amalgams. Clinical Significance: People affected by Multiple Chemical Sensitivity deserve the attention, understanding and help of health professionals and family members, to face an invisible illness for those who do not suffer from it. Support is needed and doctors

关键词： Chemical Sensitivity Electromagnetic Sensitivity Mercury Poisoning Amalgams QEESI

Life-threatening bleeding caused by artery pseudoaneurysm after endoscopic procedure successfully treated by artery embolization

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World Journal of Clinical Cases 2025年第13期13卷 52-55页

作者： Sergio Pérez-Holanda Office of Regional Vice-ministry of Health Regional Vice-ministry of HealthOviedo 33005AsturiasSpain

The Kakinuma et al’s case report shows that non-pregnancy-related arterial pseudoaneurysm is a relatively rare,little known by some gynecologists,endo-scopists,surgeons or radiologists,which can cause massive *** pseudoaneurysm is a condition in which the wall of a blood vessel collapses due to some invasive event,and the resulting leaked blood is engulfed by soft tissues,forming a cavity that is in communication with the *** is a potentially life-threatening complication that could occurs after some deliveries and some gynecological invasive ***,an undetermined percentage of pseudoaneurysms are asymptomatic,and in an asymptomatic patient it is difficult to predict the risk of haemorrhage and the attitude to follow,which depends on several factors,such as,the size and location of the vessel involved,changes in the size of the pseudoaneurysm,or the available therapeutic resources to be offered to patients,among others *** management of abdominal arterial pseudoaneurysm does not have consistent scientific evidence,but it seems that,regardless of the associated circumstances,the pseudoaneurysm could be treated at least initially,and mainly,through endovascular procedures,as done by Kakinuma et al.

关键词： Aneurysm False Computed tomography angiography Transarterial embolization Uterine artery Uterine artery embolization Uterine pseudoaneurysm

SEM Investigation of the Microstructure of Oxygen-Deficient Ca2FeGaO6-δ

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Journal of Materials Science and Chemical Engineering 2025年第1期13卷 1-6页

作者： Ariella Fogel Mandy Guinn ram Krishna Hona Environmental Science Department United Tribes Technical College Bismarck USA

This study presents a detailed investigation of the microstructure of the oxygen-deficient perovskite material Ca2FeGaO6-δ using Scanning Electron Microscopy (SEM). The material exhibits significant porosity and irregular grain morphology, with variations in grain size and growth. Unlike conventional perovskite structures, Ca2FeGaO6-δ shows non-uniform grain development, which can be attributed to the presence of oxygen vacancies (δ). SEM analysis reveals that the irregularities in grain size and shape, coupled with the porous nature of the material, are likely to influence its functional properties. These findings provide valuable insights into the structural features of Ca2FeGaO6-δ, offering a foundation for understanding its potential applications in catalysis, sensors, and other technologies. The study highlights the critical role of microstructural characteristics in determining the material’s performance.

关键词： XRD Solid-State Reaction Perovskite Oxides Oxygen Deficiency SEM