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Hepatitis C virus-specific cytotoxic T cell response restoration after treatment-induced hepatitis C virus control

World Journal of Gastroenterology 2015年第12期21卷 3480-3491页

作者： Juan-Ramón Larrubia Elia Moreno-Cubero Joaquín Miquel Eduardo sanz-de-Villalobos Translational Hepatology Unit Guadalajara University Hospital University of Alcalá Department of Medicine and Medical Specialties University of Alcalá Department of Biology of Systems University of Alcalá

Hepatitis C virus(HCV)-specific cytotoxic T cell(CTL) response plays a major role in viral control during spontaneous infection resolution. These cells develop an exhausted and pro-apoptotic status during chronic onset, being unable to get rid of HCV. The role of this response in contributing to sustained viral response(SVR) after anti-HCV is controversial. Recent studies show that after successful interferon-based anti-HCV treatment, HCV traces are still detectable and this correlates with a peak of HCV-specific CTL response activation, probably responsible for maintaining SVR by subsequent complete HCV clearing. Moreover, SVR patients' serum is still able to induce HCV infection in na?ve chimpanzees, suggesting that the infection could be under the control of the immune system after a successful treatment, being transmissible in absence of this adaptive response. At least theoretically, treatmentinduced viral load decrease could allow an effective HCV-specific CTL response reestablishment. This effect has been recently described with anti-HCV interferonfree regimes, based on direct-acting antivirals. Nevertheless, this is to some extent controversial with interferon-based therapies, due to the detrimental immunoregulatory α-interferon effect on T cells. Moreover, HCV-specific CTL response features during anti-HCV treatment could be a predictive factor of SVR that could have clinical implications in patient management. In this review, the recent knowledge about the role of HCV-specific CTL response in the development of SVR after anti-HCV treatment is discussed.

关键词： Hepatitis C virus Chronic hepatitis Hepatitis C vi

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Does a Country/Region's Economic Status Affect Its Universities' Presence in International Rankings?

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Journal of Data and Information Science 2019年第2期4卷 56-78页

作者： Esteban Fernandez Tuesta Carlos Garcia-Zorita Rosario Romera Ayllon Elias sanz-Casado Escola de Artes Ciencias e HumanidadesUniversidade de Sao PauloBrazil Department of Library Science and Documentation Carlos III University of MadridSpain Laboratory of Metric Studies on Information(LEMI) Carlos III University of MadridSpain Research Institute for Higher Education and Science(INAECU) MadridSpain Associated Unit IFS(CSIC)-LEMI(UC3M) Carlos III University of MadridSpain Department of Statistics Carlos III University of MadridSpain

Purpose: Study how economic parameters affect positions in the Academic Ranking of World Universities' top 500 published by the Shanghai Jiao Tong University Graduate School of Education in countries/regions with listed higher education institutions. Design/methodology/approach: The methodology used capitalises on the multi-variate characteristics of the data analysed. The multi-colinearity problem posed is solved by running principal components prior to regression analysis, using both classical(OLS) and robust(Huber and Tukey) methods. Findings: Our results revealed that countries/regions with long ranking traditions are highly competitive. Findings also showed that some countries/regions such as Germany, United Kingdom, Canada, and Italy, had a larger number of universities in the top positions than predicted by the regression model. In contrast, for Japan, a country where social and economic performance is high, the number of ARWU universities projected by the model was much larger than the actual figure. In much the same vein, countries/regions that invest heavily in education, such as Japan and Denmark, had lower than expected *** limitations: Using data from only one ranking is a limitation of this study, but the methodology used could be useful to other global rankings. Practical implications: The results provide good insights for policy makers. They indicate the existence of a relationship between research output and the number of universities per million inhabitants. Countries/regions, which have historically prioritised higher education, exhibited highest values for indicators that compose the rankings methodology; furthermore,minimum increase in welfare indicators could exhibited significant rises in the presence of their universities on the ***/value: This study is well defined and the result answers important questions about characteristics of countries/regions and their higher education system.

关键词： Academic Ranking of World Universities Socio-economic indicators Regression analysis

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Bone marrow-derived mononuclear stem cells in the treatment of retinal degenerations

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Neural Regeneration Research 2022年第9期17卷 1937-1944页

作者： Diego García-Ayuso Johnny Di Pierdomenico David García-Bernal Manuel Vidal-sanz María P.Villegas-Pérez Departamento de Oftalmología Facultad de MedicinaUniversidad de MurciaCampus de Ciencias de la saludMurciaSpain Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca(IMIB-Virgen de la Arrixaca) MurciaSpain Servicio de Hematología Hospital Clínico Universitario Virgen de la ArrixacaMurciaSpain

Retinal degenerative diseases affecting the outer retina in its many forms(inherited,acquired or induced)are characterized by photoreceptor loss,and represent currently a leading cause of irreversible vision loss in the *** present,there are very few treatments capable of preventing,recovering or reversing photoreceptor degeneration or the secondary retinal remodeling,which follows photoreceptor loss and can also cause the death of other retinal ***,these diseases are nowadays one of the greatest challenges in the field of ophthalmological *** marrow derived-mononuclear stem cell transplantation has shown promising results for the treatment of photoreceptor *** cells may have the potential to slow down photoreceptor loss,and therefore should be applied in the early stages of photoreceptor ***,because of their possible paracrine effects,they may have a wide range of clinical applications,since they can potentially impact on several retinal cell types at once and photoreceptor degenerations can involve different cells and/or begin in one cell type and then affect adjacent *** intraocular injection of bone marrow derived-mononuclear stem cells also enhances the outcomes of other treatments aimed to protect ***,it is likely that future investigations may combine bone marrow derived-mononuclear stem cell therapy with other systemic or intraocular treatments to obtain greater therapeutic effects in degenerative retinal diseases.

关键词： age-related macular degeneration bone marrow stem cells intravitreal injection macroglia microglia photoreceptor degeneration retinal ganglion cells retinitis pigmentosa subretinal injection transplant

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Telomerase activity in colorectal cancer,prognostic factor and implications in the microsatellite instability pathway

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World Journal of Gastroenterology 2007年第28期13卷 3868-3872页

作者： M Vidaurreta ML Maestro S Rafael S Veganzones MT sanz-Casla J Cerdán M Arroyo Servicio de Análisis Clínicos Hospital Clínico San CarlosMadrid 28040Spain Servicio de Análisis Clínicos Hospital Clínico San CarlosMadrid 28040Spain Servicio de Cirugía General ⅢHospital Clínico San CarlosMadrid 28040Spain

AIM： To determine whether the telomerase activity is related to the Microsatellite instability （MSI） genetic pathway and whether it means a difference in the survival.METHODS： The population consisted of 97 colorectal cancer patients. MSI determination was performed in accordance with the NCI criteria using PCR and Genescan. Telomerase activity was determined by the TRAP-assay, an ELISA procedure based on the amplification of telomeric repeat sequences.RESULTS： 6.2% showed high MSI （MSI-H）, 10.3% showed low MSI （MSI-L） and 83.5% did not show this alteration （MSS）. Positive telomerase activity was detected in 92.8% of the patients. 83.3% of MSI-H tumors showed positive telomerase against 93.8% of MSS tumors. In the overall survival analysis the absence of telomerase activity conferred a better prognosis.CONCLUSION： Previous works have shown that tumors which develop via the MSI pathway present a better prognosis. No link between telomerase activity and MSl status is observed, although sample sizes are small. Patients with telomerase negative tumors had better overall survival than patients with telomerase positive tumors.

关键词： Microsatellite instability Telomerase Colorectal cancer Prognosis

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Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery-design,characterization,and biological insights

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Nano Research 2024年第10期17卷 9111-9125页

作者： Ana M.López-Estévez Y.Zhang María medel Iker Arriaga Lucía Sanjurjo Cristian Huck-Iriart Nicola G.A.Abrescia María J.Vicent Defang Ouyang Dolores Torres María José Alonso Center for Research in Molecular Medicine and Chronic Diseases(CiMUS) University of Santiago de CompostelaSantiago de Compostela 15782Spain Department of Pharmacology Pharmacy and Pharmaceutical TechnologySchool of PharmacyUniversity of Santiago de CompostelaSantiago de Compostela 15782Spain Health Research Institute of Santiago de Compostela(IDIS) Santiago de Compostela 15782Spain State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Polymer Therapeutics Laboratory and CIBERONC Prince Felipe Research Centre Valencia E-46012Spain Structure and Cell Biology of Viruses Lab CIC bioGUNEBasque Research and Technology Alliance(BRTA)Derio 48160Spain ALBA Synchrotron Light Source Experiments DivisionCerdanyola del VallèsBarcelona 08290Spain IKERBASQUE Basque Foundation for ScienceBilbao 48009Spain

The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies(mAbs).Despite their increasing potential,mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular *** offers promising solutions to overcome this limitation,however,formulation challenges *** challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the complex formulation methods,and the insufficient characterization of mAb-loaded ***,we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies(HANAs)specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity(50%,w/w).HANAs composed by an mAb,modified HA and phosphatidylcholine(PC)resulted in sizes of~100 nm and neutral surface *** modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and *** composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy(cryo-TEM),asymmetrical flow field-flow fractionation(AF4),and small-angle X-ray scattering(SAXS).These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic *** vitro experiments in cancer cell lines and macrophages confirmed HANAs’low toxicity and ability to transport mAbs to the intracellular *** reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was *** conclusion,these results underscore the suitability of HANAs technology to load and deliver biologicals,which holds promise for future clinical translation.

关键词： monoclonal antibody nanoparticles hyaluronic acid characterization particle size computational modeling

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Retinal remodeling following photoreceptor degeneration causes retinal ganglion cell death

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Neural Regeneration Research 2018年第11期13卷 1885-1886页

作者： Diego Garcia-Ayuso Johnny Di Pierdomenico Marta Agudo-Barriuso Manuel Vidal-sanz Maria P. ViUegas-Perez Departamento de Oftalmologla Facultad de Medicina Universidad de Murcia and Instituto Murciano de Investigacion Biosanitaria Hospital Virgen de la Arrixaca (IMIB-Virgen de la Arrixaca) Murcia Spain

The retina is the extension of the central nervous system that senses *** and rods,situated in the outer retina,convert light into electrical signals that travel through intermediate neurons where these are further pr... 详细信息

关键词： FG Retinal remodeling following photoreceptor degeneration causes retinal ganglion cell death Figure

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Role of microglial cells in photoreceptor degeneration

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Neural Regeneration Research 2019年第7期14卷 1186-1190页

作者： Johnny Di Pierdomenico Diego García-Ayuso Marta Agudo-Barriuso Manuel Vidal-sanz María Paz Villegas-Pérez Departamento de Oftalmología Facultad de MedicinaUniversidad de Murciaand Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca(IMIB-Virgen de la Arrixaca)

Inherited photoreceptor degeneration in humans constitutes a major cause of irreversible blindness in the *** comprise various diseases,but retinitis pigmentosa is the most frequently *** pigmentosa is commonly limited to the eye,where there is progressive photoreceptor degeneration,rods and secondarily *** mechanisms of cone and rod degeneration continue to be investigated,since most of the mutations causing retinitis pigmentosa affect rods and thus,the secondary death of cones is an intriguing question but,ultimately,the cause of *** the mechanisms of rod and cone degeneration could help us to develop therapies to stop or,at least,slow down the degeneration *** cone degeneration has been attributed to the trophic dependence between rods and cones,but microglial cell activation could also have a *** this review,based on previous work carried out in our laboratory in early stages of photoreceptor degeneration in two animal models of retinitis pigmentosa,we show that microglial cell activation is observed prior to the the initiation of photoreceptor *** also show that there is an increase of the retinal microglial cell densities and invasion of the outer retinal layers by microglial *** inhibition of the microglial cells improves photoreceptor survival and morphology,documenting a role for microglial cells in photoreceptor ***,these results indicate that the modulation of microglial cell reactivity can be used to prevent or diminish photoreceptor death in inherited photoreceptor degenerations.

关键词： Royal College of Surgeons RCS P23H-1 microglia minocycline photoreceptor retinal degeneration retinitis pigmentosa

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Characterization of glutamatergic VTA neural population responses to aversive and rewarding conditioning in freely-moving mice

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Science Bulletin 2019年第16期64卷 1167-1178页

作者： Quentin Montardy Zheng Zhou Zhuogui Lei Xuemei Liu Pengyu Zeng Chen Chen Yuanming Liu Paula sanz-Leon Kang Huang Liping Wang Shenzhen Key Lab of Neuropsychiatric Modulation and Collaborative Innovation Center for Brain Science Guangdong Provincial Key Laboratory of Brain Connectome and BehaviorCAS Center for Excellence in Brain Science and Intelligence TechnologyThe Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsShenzhen 518055China University of Chinese Academy of Sciences Beijing 100049China School of Physics the University of SydneySydney 2006Australia Centre for Integrative Brain Function the University of SydneySydney 2006Australia Department of Biomedical Sciences City University of Hong KongTat Chee AvenueKowloonHong KongSAR 999077China

The Ventral Tegmental Area(VTA) is a midbrain structure known to integrate aversive and rewarding stimuli, but little is known about the role of VTA glutamatergic(VGluT2) neurons in these *** activation of VGluT2 soma evokes rewarding behaviors, while activation of their downstream projections evokes aversive behaviors. To facilitate our understanding of these conflicting properties, we recorded calcium signals from VTAVGluT2+ neurons using fiber photometry in VGluT2-cre mice to investigate how this population was recruited by aversive and rewarding stimulation, both during unconditioned and conditioned protocols. Our results revealed that, as a population, VTAVGluT2+neurons responded similarly to unconditioned-aversive and unconditioned-rewarding stimulation. During aversive and rewarding conditioning, the CS-evoked responses gradually increased across trials whilst the US-evoked response remained stable. Retrieval 24 h after conditioning, during which mice received only CS presentation, resulted in VTAVGluT2+ neurons strongly responding to CS presentation and to the expected-US but only for aversive conditioning. To help understand these differences based on VTAVGluT2+ neuronal networks, the inputs and outputs of VTAVGluT2+ neurons were investigated using Cholera Toxin B(CTB) and rabies virus. Based on our results, we propose that the divergent VTAVGluT2+ neuronal responses to aversion and reward conditioning may be partly due to the existence of VTAVGluT2+ subpopulations that are characterized by their connectivity.

关键词： Ventral Tegmental Area Aversion Reward Conditioning Behavior

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Role of chemokines and their receptors in viral persistence and liver damage during chronic hepatitis C virus infection

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World Journal of Gastroenterology 2008年第47期14卷 7149-7159页

作者： Juan R Larrubia Selma Benito-Martínez Miryam Calvino Eduardo sanz-de-Villalobos Trinidad Parra-Cid Department of Gastroenterology Guadalajara University HospitalUniversity of AlcaláDonante de Sangre st.19002 GuadalajaraSpain Guadalajara University Hospital University of AlcaláDonante de Sangre st.19002 GuadalajaraSpain

Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected *** milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell(Th1/Tc1) *** chemokines consist of CCL3(macrophage inflammatory protein-1α;MIP-1α),CCL4(MIP-1β),CCL5(regulated on activation normal T cell expressed and secreted;RANTES),CXCL10(interferon-γ-inducible protein-10;IP-10),CXCL11(interferon-inducible T-cell α chemoattractant;I-TAC),and CXCL9(monokine induced by interferon γ;Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine *** and peripheral blood levels of these chemokines are increased during chronic hepatitis *** interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the *** the adaptive immune response fails in this task,non-specific T cells without the capacity to control the infection are also recruited to the liver,and these are ultimately responsible for the persistent hepatic *** modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection,and to maintain liver viability during the chronic phase,by impairing non-specific T cell *** chemokines and their receptors correlate with liver damage,and CXCL10(IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response *** regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.

关键词： Chemokines Chemokine receptors Hepatitis C virus Viral hepatitis pathogenesis Persistentinfection Viral escape mechanism

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Kinetic study and kinetic parameters of lipase-catalyzed glycerolysis of sardine oil in a homogeneous medium

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Chinese Journal of Catalysis 2016年第4期37卷 596-606页

作者： Angela García Solaesa María Teresa sanz Sagrario Beltrán Rodrigo Melgosa 布尔戈斯大学生物技术与食品科学系(化学工程部) 西班牙布尔戈斯09001

The production of polyunsaturated fatty acids （PUFAs） concentrates by enzymatic catalysis has gained interest due to their stereospecificity and the milder conditions employed compared to the use of inorganic catalysts. The enzymatic glycerolysis of sardine oil by Lipozymeò435 to get PUFA concentrates in the forms of di‐and monoacylglycerols （DAGs, MAGs） in an optimized amount of tert‐butanol as the organic solvent was studied. First, mass transfer limitation of the reaction sys‐tem was analyzed. The effects of different operating variables such as lipase loading, temperature and feed composition were investigated. A semi‐empirical kinetic model based on the reversible elementary reactions of glycerolysis and hydrolysis of the glycerides was employed to correlate the experimental kinetic data. A molar ratio glycerol：oil of 3：1 was the optimum, which produced more than 84 wt%of MAG at 323 K. A comparison with other glycerolysis systems was performed using MAG yield, reaction rate and significance of kinetic parameters.

关键词： Lipase Glycerolysis Tert-butanol Mass transfer Kinetic model

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