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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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Mesenchymal stem cell therapy in retinal and optic nerve diseases: An update of clinical trials

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World Journal of Stem Cells 2016年第11期8卷 376-383页

作者： Sonia labrador-Velandia María Luz Alonso-Alonso sara Alvarez-Sanchez Jorge González-Zamora Irene Carretero-Barrio José Carlos Pastor Iván Fernandez-Bueno Girish Kumar Srivastava Instituto Universitario de Oftalmobiología Aplicada Universidad de Valladolid 47011 Valladolid Spain Facultad de Medicina Universidad de Valladolid 47005 Valladolid Spain Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León 47011 Valladolid Spain Red Temática de Investigación Cooperativa Sanitaria del Instituto de Salud Carlos Ⅲ. Oftared 28029 Madrid Spain Hospital Clínico Universitario de Valladolid 47003 Valladolid Spain

Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advances in the knowledge of neuroprotection, immunomodulation and regenerative properties of mesenchymal stem cells(MSCs) have been obtained by several preclinical studies of various neurodegenerative diseases. It has provided the opportunity to perform the translation of this knowledge to prospective treatment approaches for clinical practice. Since 2008, several first steps projecting new treatment approaches, have been taken regarding the use of cell therapy in patients with neurodegenerative pathologies of optic nerve and retina. Most of the clinical trials using MSCs are in Ⅰ/Ⅱ phase, recruiting patients or ongoing, and they have as main objective the safety assessment of MSCs using various routes of administration. However, it is important to recognize that, there is still a long way to go to reach clinical trials phase Ⅲ-Ⅳ. Hence, it is necessary to continue preclinical and clinical studies to improve this new therapeutic tool. This paper reviews the latest progress of MSCs in human clinical trials for retinal and optic nerve diseases.

关键词： Mesenchymal stem cells Cell therapy Optic nerve diseases Clinical trials Retinal diseases

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Magnetic resonance imaging for prostate cancer before radical and salvage radiotherapy: What radiation oncologists need to know

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World Journal of Clinical Oncology 2017年第4期8卷 305-319页

作者： Felipe Cou?ago Gemma Sancho Violeta Catalá Diana Hernández Manuel Recio sara Montemui?o Jhonathan Alejandro Hernández Antonio Maldonado Elia del Cerro Department of Radiation Oncology Hospital Universitario Quirónsalud Madrid Clinical Department Faculty of BiomedicineUniversidad Europea Department of Radiation Oncology Hospital de la Santa Creu i Sant Pau Department of Radiology Fundació Puigvert Department of Radiology Hospital de la Santa Creu i Sant Pau Department of Radiology Hospital Universitario Quirónsalud Madrid Department of Radiation Oncology Hospital Universitario de Fuenlabrada Department of Nuclear Medicine Hospital Universitario Quirónsalud Madrid

External beam radiotherapy(EBRT) is one of the principal curative treatments for patients with prostate cancer(PCa). Risk group classification is based on prostate-specific antigen(PSA) level, Gleason score, and T-stage. After risk group determination, the treatment volume and dose are defined and androgen deprivation therapy is prescribed, if appropriate. Traditionally, imaging has played only a minor role in T-staging due to the low diagnostic accuracy of conventional imaging strategies such as transrectal ultrasound, computed tomography, and morphologic magnetic resonance imaging(MRI). As a result, a notable percentage of tumours are understaged, leading to inappropriate and imprecise EBRT. The development of multiparametric MRI(mp MRI), an imaging technique that combines morphologic studies with functional diffusion-weighted sequences and dynamic contrastenhanced imaging, has revolutionized the diagnosis and management of PCa. As a result, mpM RI is now used in staging PCa prior to EBRT, with possible implications for both risk group classification and treatment decisionmaking for EBRT. mpM RI is also being used in salvageradiotherapy(SRT), the treatment of choice for patients who develop biochemical recurrence after radical prostatectomy. In the clinical context of biochemical relapse, it is essential to accurately determine the site of recurrence-pelvic(local, nodal, or bone) or distant-in order to select the optimal therapeutic management approach. Studies have demonstrated the value of mpM RI in detecting local recurrences-even in patients with low PSA levels(0.3-0.5 ng/m L)-and in diagnosing bone and nodal metastasis. The main objective of this review is to update the role of mpM RI prior to radical EBRT or SRT. We also consider future directions for the use and development of MRI in the field of radiation oncology.

关键词： Prostate cancer Staging Radical radiotherapy Multiparametric magnetic resonance imaging Biochemical failure Radical prostatectomy Salvage radiotherapy

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Preclinical evaluation of azathioprine plus buthionine sulfoximine in the treatment of human hepatocarcinoma and colon carcinoma

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World Journal of Gastroenterology 2011年第34期17卷 3899-3911页

作者： Borja Hernández-Breijo Jorge Monserrat sara Ramírez-Rubio Eva P Cuevas Diana Vara Inés Díaz-laviada M Dolores Fernández-Moreno Irene D Román Javier P Gisbert Luis G Guijarro Molecular Hepatic Toxicology Unit Biochemistry and Molecular Biology Department University of Alcalá Networked Biomedical Research Center of Hepatic and Digestive Diseases (CIBEREHD) Medicine Department University of Alcalá Neuroendocrinology of Cannabinoid/Vanilloid System Unit Biochemistry and Molecular Biology Department University of Alcalá Gastroenterology Unit Hospital de la Princesa Institute of Health Research Princesa Networked Biomedical Research Center of Hepatic and Digestive Diseases (CIBEREHD)

AIM: To evaluate the efficacy and the safety of azathioprine (AZA) and buthionine sulfoximine (BSO) bylocalized application into HepG2 tumor in ***: Different hepatoma and colon carcinoma cell lines (HepG2, HuH7, Chang liver, LoVo, RKO, SW-48, SW-480) were grown in minimal essencial medium supplemented with 10% fetal bovine serum and 1% antibiotic/antimycotic solution and maintained in a humidified 37 ℃ incubator with 5% CO2. These cells were pretreated with BSO for 24 h and then with AZA for different times. We examined the effects of this combination on some proteins and on cellular death. We also studied the eff icacy and the safety of AZA (6 mg/kg per day) and BSO (90 mg/kg per day) in HepG2 tumor growth in vivo using athymic mice. We measured safety by serological markers such as aminotransferases and creatine ***: The in vitro studies revealed a new mechanism of action for the AZA plus BSO combination in the cancer cells compared with other thiopurines (6-mercaptopurine, 6-methylmercaptopurine, 6-thioguanine and 6-methylthioguanine) in combination with BSO. The cytotoxic effect of AZA plus BSO in HepG2 cells resulted from necroptosis induction in a mitochondrial-dependent manner. From kinetic studies we suggest that glutathione (GSH) depletion stimulates c-Jun amino-terminal kinase and Bax translocation in HepG2 cells with subsequent deregulation of mitochondria (cytochrome c release, loss of membrane potential), and proteolysis activation leading to loss of membrane integrity, release of lactate dehydrogenase and DNA degradation. Some of this biochemical and cellular changes could be reversed by N-acetylcysteine (a GSH replenisher). In vivo studies showed that HepG2 tumor growth was inhibited when AZA was combined with ***: Our studies suggest that a combination of AZA plus BSO could be useful for localizedtreatment of hepatocellular carcinoma as in the currently used transarterial chemoembolization method.

关键词： Azathioprine Buthionine sulfoximine Transarterial chemoembolization Glutathione Apoptosis Necrosis

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Conventional type 1 dendritic cells protect against age-related adipose tissue dysfunction and obesity

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Cellular & Molecular Immunology 2022年第2期19卷 260-275页

作者： Elena Hernández-García Francisco J.Cueto Emma C.L.Cook Ana Redondo-Urzainqui sara Charro-Zanca Iñaki Robles-Vera Ruth Conde-Garrosa Ivana Nikolić Guadalupe Sabio David Sancho Salvador Iborra Department of Immunology Ophthalmology and ENTSchool of MedicineUniversidad Complutense de MadridMadrid 28040Spain Centro Nacional de Investigaciones Cardiovasculares(CNIC) Madrid 28029Spain

Conventional dendritic cells(cDCs)scan and integrate environmental cues in almost every tissue,including exogenous metabolic *** cDCs are critical in maintaining immune balance,their role in preserving energy homeostasis is ***,we showed that Batf3-deficient mice lacking conventional type 1 DCs(cDC1s)had increased body weight and adiposity during *** led to impaired energy expenditure and glucose tolerance,insulin resistance,dyslipidemia,and liver ***1 deficiency caused adipose tissue inflammation that was preceded by a paucity of NK1.1+invariant NKT(iNKT)***,among antigen-presenting cells,cDC1s exhibited notable induction of IFN-γproduction by iNKT cells,which plays a metabolically protective role in lean adipose ***3L treatment,which expands the dendritic cell(DC)compartment,mitigated diet-induced obesity and hyperlipidemia in a Batf3-dependent *** effect was partially mediated by NK1.1+*** results reveal a new critical role for the cDC1-iNKT cell axis in the regulation of adipose tissue homeostasis.

关键词： Dendritic Cells NKT Obesity ageing FLT3L

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Characterization of the Constructions Materials Used in the Hydroelectric Power Plants in the Sedano＇s Valley, Burgos （Spain）

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Journal of Civil Engineering and Architecture 2011年第10期5卷 903-909页

作者： sara Gutierrez Gonzailezt Jesus Gadea Sainz Angel Rodriguez Saiz Carlos Junco Petrement Department of Construction Engineering High Polytechnic School University of Burgos Spain

Small hydropower plants for electricity generation were first built in Spain in the early 1880s. The Spanish peninsula is characterized by its rugged landscape, fast flowing rivers and steep gradients. A clear example of this is the remarkable area of the upper Ebro river basin where powerful water flows are found that are ideal for electricity generation. Between 1900 and 1930, the river Ebro was a major source of energy for industrial areas such as Alava, Vizcaya, Vitoria, Miranda de Ebro, Burgos and la Rioja. Between 1951-1965, the use of these small hydropower plants declined due to the construction of alternatives by industrialists in the Basque Country, which in most cases led to their deterioration. They were rescued in the late twentieth century, thanks to private sector initiatives which funded their rehabilitation. This study examines two small-scale hydraulic power plants in the province of Burgos at Medina de Pomar and at Quintanilla Escalada; both buildings were used for generating electricity and had living quarters for the workers and now represent historic architectonic and industrial heritage. The study documents their architectonic features and the restoration processes that have permitted one of them to remain in operation up until the present day.

关键词： Small hydropower plants local materials rehabilitation industrial heritage.

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Study of Variation in Phosphocalcic Metabolism during Pregnancy and Postpartum in the Holstein Cow of Constantine Region

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Journal of Pharmacy and Pharmacology 2017年第8期5卷 526-530页

作者： Selma Benhizia Mohamed Amir Boudhene sara Benayache Nadjoua Arzour Abdeslam Mekroud laboratoire de recherche de pathologies animales developpement des Olevages et surveillance de la chaine alimentaire desdenr~es animales ou d'origine animale lnstitut des sciences vOt~rinaires route de Guelma el-khroub. Constantine 05. 25000Algeria. laboratoire GSPA Institut des sciences veterinaires route de Guelma el-khroub Constantine 05. 25000 Algeria

Pregnancy, parturition, and lactation represent physiological changes of organism, which activates adaptation mechanismsdedicated to maintain homeostasis during peripartum period. Despite of the appropriate input of calcium and phosphorus, thehomeostasis of phosphocalcic metabolism is sometimes faulty, in particular among animals with high production potential. The aim ofthis study is to define usual values of calcium and phosphorus during pregnancy and postpartum period. This paraclinic tool will serveto a good interpretation when used by veterinarians. A second goal is to study the influence of physiological stage on phosphocalcicmetabolism in milch cow. The hereby study was conducted on 17 Prim＇ Holsteins cow breed from 3 to 5 years old, clinically healthy,multiparous and derived from two dairy farms located in the wilaya of Constantine. Blood samples were taken from the jugular veinusing dry tubes at different physiological stages （early gestation, mid gestation, late gestation, pre-partum, one day after parturition, andone month postpartum）. All of the samples correctly identified were transported to a specialized laboratory where specific kits wereused. Blood calcium and phosphorus levels have significantly varied depending on physiological stage （p 〈 0.01）. They showed a highpre-partum variation, with a rate of 94.71 mg/mL and 61.99 mg/mL, respectively. These results can be used as means of follow-upreproduction for a better management of dairy fanning.

关键词： Calcium Blood level, phosphorus blood level, milch cow, gestation, postpartum.

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Cystic fibrosis transmembrane conductance regulator functional evaluations in a G542X+/-IVS8Tn:T7/9 patient with acute recurrent pancreatitis

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World Journal of Clinical Cases 2019年第22期7卷 3757-3764页

作者： sara Caldrer Gabriella Bergamini Angela Sandri Silvia Vercellone Luca Rodella Angelo Cerofolini Francesco Tomba Filippo Catalano Luca Frulloni Mario Buffelli Gloria Tridello Hugo de Jonge Baroukh Maurice Assael Claudio Sorio Paola Melotti Department of Medicine General Pathology DivisionCystic Fibrosis Translational Research Laboratory“D.Lissandrini”University of VeronaVerona 37134Italy Cystic Fibrosis Center Azienda Ospedaliera Universitaria Integrata VeronaVerona 37126Italy Endoscopic Surgery Unit Azienda Ospedaliera Universitaria Integrata VeronaVerona 37126Italy Department of Medicine Pancreas CenterUniversity of VeronaVerona 37134Italy Department of Neurosciences Biomedicine and Movement SciencesPhysiology Section UniversityVerona 37126Italy Gastroenterology and Hepatology Erasmus University Medical CenterRotterdam 3015Netherlands

BACKGROUND Acute recurrent pancreatitis(ARP)is characterized by episodes of acute pancreatitis in an otherwise normal *** no cause of ARP is identifiable,the diagnosis of"idiopathic"ARP is *** in the cystic fibrosis transmembrane conductance regulator(CFTR)gene increase the risk of ARP by 3-to 4-times compared to the general population,while cystic fibrosis(CF)patients present with a 40-to 80-times higher risk of developing *** SUMMARY In non-classical CF or CFTR-related disorders,CFTR functional tests can help to ensure a proper *** applied an individualized combination of standardized and new CFTR functional bioassays for a patient referred to the Verona CF Center for evaluation after several episodes of acute *** CFTR genotype was G542X+/-with IVS8Tn:T7/9 *** sweat(Cl-)values were *** current measurements were performed according to the European Cystic Fibrosis Society Standardized Operating *** nasal surgery for deviated septum did not allow for nasal potential difference *** function and sputum cultures were normal;azoospermia was *** divisum was excluded by imaging but hypoplasia of the left hepatic lobe was *** tests applied in this case include sweat rate measurement by image analysis,CFTR function in monocytes evaluated using a membrane potential-sensitive fluorescent probe,and the intestinal organoids forskolin-induced swelling *** Combination of innovative CFTR functional assays might support a controversial diagnosis when CFTR-related disorders and/or non-classical CF are suspected.

关键词： Recurrent acute pancreatitis Cystic fibrosis Cystic fibrosis transmembraneconductance regulator function Intestinal current Organoids Sweat test Controversialdiagnosis Case report

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Multiscale computational understanding and growth of 2D materials:a review

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npj Computational Materials 2020年第1期6卷 1484-1501页

作者： Kasra Momeni Yanzhou Ji Yuanxi Wang Shiddartha Paul sara Neshani Dundar E.Yilmaz Yun Kyung Shin Difan Zhang Jin-Wu Jiang Harold S.Park Susan Sinnott Adri van Duin Vincent Crespi Long-Qing Chen Mechanical Engineering Department Louisiana Tech UniversityRustonLA 71272USA Department of Mechanical Engineering University of AlabamaTuscaloosaALUSA Institute for Micromanufacturing Louisiana Tech UniversityRustonLAUSA Materials Research Institute The Pennsylvania State UniversityUniversity ParkPA 16802USA Department of Materials Science and Engineering The Pennsylvania State UniversityUniversity ParkPA 16802USA 2-Dimensional Crystal Consortium The Pennsylvania State UniversityUniversity ParkPA 16802USA Department of Physics The Pennsylvania State UniversityUniversity ParkPA 16802USA Department of Electrical Engineering Iowa State UniversityAmesIA 50010USA Mechanical Engineering Department The Pennsylvania State UniversityUniversity ParkPA 16802USA Shanghai Institute of Applied Mathematics and Mechanics Shanghai Key Laboratory of Mechanics in Energy EngineeringShanghai UniversityShanghai 200072China Department of Mechanical Engineering Boston UniversityBostonMA 02215USA Department of Engineering Science and Mechanics The Pennsylvania State UniversityUniversity ParkPA 16802USA Department of Mathematics The Pennsylvania State UniversityUniversity ParkPA 16802USA

The successful discovery and isolation of graphene in 2004,and the subsequent synthesis of layered semiconductors and heterostructures beyond graphene have led to the exploding field of two-dimensional(2D)materials that explore their growth,new atomic-scale physics,and potential device *** review aims to provide an overview of theoretical,computational,and machine learning methods and tools at multiple length and time scales,and discuss how they can be utilized to assist/guide the design and synthesis of 2D materials beyond graphene.

关键词： synthesis utilized subsequent

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Estimation of la1-xSrxMnO3(x=0.15～0.5) Emittance by Thermal Irradiation Theory

Estimation of La1-xSrxMnO3(x=0.15～0.5) Emittance by Thermal...

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2012 International Conference on Mechanical Materials and Manufacturing Engineering(ICMMME 2012)

作者： sara Hatefi Monfared Guangze Tang Xinxin Ma Fereidoun A.Mianji School of Materials Science & Engineering Harbin Institute of Technology National Key laboratory of Science and Technology on Precision Hot Processing of Metals Harbin Institute of Technology State Key laboratory of Advanced Welding and Joining Harbin Institute of Technology

laSrMnO(LSMO) has recently shown promising features as a metal-insulator material over a limited range of Sr doping(x=0.175 to 0.25). Its thermal property has been commonly measured through the very expensive calorimetric method. In this paper, a considerably more convenient thermal investigation approach to this issue through the thermal irradiation theory is proposed. LSMO compounds were synthesized with a wide range of x(0.15 to 0.5) using the precisely controlled Pechini sol-gel method. XRD phase structure analysis and XPS composition and chemical state study were adopted for quality assurance of the compounds. Resistance and infrared reflectance of the samples were measured respectively with the help of the four probe technique in temperature range of 150 K to 380 K and an infrared spectrometer over a temperature range of 153 K to 544 K. Investigations showed a good correlation between these two measures approving the metal-insulator characteristic of all the samples. Calculation of the total normal emittance(ε(T)) of the compounds was innovatively simplified using the measured reflectivity data through the thermal irradiation theory for graybody. Moreover, the results showed that every x ratio fabricated through the precisely controlled Pechini method presented a unique ε(T) characteristic with a different metal-insulator transition temperature.

关键词： Composite materials Nanostructured matereials Optical properties Rare earth alloys and compounds Sol-gel processes Thermal analysis

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