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Taking advantage of the potential of mesenchymal stromal cells in liver regeneration:Cells and extracellular vesicles as therapeutic strategies

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World Journal of Gastroenterology 2018年第23期24卷 2427-2440页

作者： Esteban Juan Fiore Luciana María domínguez Juan Bayo Mariana Gabriela García Guillermo Daniel Mazzolini Laboratory of Gene Therapy Instituto de Investigaciones en Medicina TraslacionalCONICET-Universidad Austral

Cell-based therapies for acute and chronic liver diseases are under continuous progress. Mesenchymal stem/stromal cells(MSCs) are multipotent cells able to migrate selectively to damaged tissue and contribute to its healing and regeneration. The MSC pro-regenerative effect occurs due to their immunomodulatory capacity and their ability to produce factors that promote cell protection and survival. Likewise,it has been observed that part of their paracrine effect is mediated by MSC-derived extracellular vesicles(EVs). EVs contain proteins,lipids and nucleic acids(DNA,m RNA,mi RNA,lnc RNA) from the cell of origin,allowing for intercellular communication. Recently,different studies have demonstrated that MSC-derived EVs could reproduce,at least in part,the biological effects obtained by MSCbased therapies. Moreover,due to EVs' stability for long periods of time and easy isolation methods they have become a therapeutic option to MSCs treatments. This review summarizes the latest results achieved in clinical trials using MSCs as cell therapy for liver regeneration,the role of EVs in liver physiopathology and the potential of MSC-derived EVs as intercellular mediators and therapeutic tools in liver diseases.

关键词： Mesenchymal stem cells Extracellular vesicles Cirrhosis Liver Acute damage Regeneration

Is interferon-beta an alternative treatment for chronic hepatitis C?

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World Journal of Gastroenterology 2006年第17期12卷 2730-2736页

作者： Ricardo Moreno-Otero María Trapero-Marugán Elena Gómez-domínguez Luisa García-Buey JoséA Moreno-Monteagudo Unit of Hepatology Hospital Universitario de La Princesa Universidad Autónoma de MadridSpain

The treatment of chronic hepatitis C （CHC） is still far from optimal, particularly for those subpopulations that do not respond to the standard combination therapy with Interferon-α （IFNα） plus ribavirin. Although in some cases the use of higher doses or longer treatment periods may be effective, these approaches are generally associated with a higher incidence of adverse events, which may either lead to a reduction in patient compliance or require drug withdrawal. IFNβ could represent an interesting alternative for treating CHC patients. Controversial data about IFNβ efficacy in CHC exist, the main reason being that many results stem from pilot studies with small cohorts of patients. However, promising results have been obtained in some subgroups of patients that fail to respond to IFNα. Additionally, the good tolerability of IFNβ represents an important advantage of the drug. The rates of dropouts in controlled clinical trials, as well as the need for dose reductions or treatment discontinuation are very low. It might be worth assessing the value of IFNβ plus ribavirin in randomized studies with a larger cohort of patients, not eligible or not tolerating standard therapy, and for non-responders.

关键词： Hepatitis C Hepatitis C virus Interferon beta Ribavirin

Impact of chitosan-based nanocarriers on cytoskeleton dynamics:Current status and challenges

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BIOCELL 2022年第4期46卷 885-891页

作者： M.CAROLINA DI SANTO AGUSTINA ALAIMO ANA PAULA domÍnguez RUBIO OSCAR E.PÉREZ Departamento de Química Biológica Facultad de Ciencias Exactas y NaturalesUniversidad de Buenos AiresBuenos AiresArgentina Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales Consejo Nacional de Investigaciones Científicas y Técnicas(IQUIBICENCONICET)Buenos AiresArgentina

Chitosan-based nanocarriers(CS-NCs)show a promising role in improving drugs and bioactive compounds delivery for ***,the effects exerted by CS-NCs at the cellular level,including their recognition and uptake,have not been fully investigated *** factors,including size,shape,concentration,and surface chemistry of CS-NCs,play an important role in determining the types of intracellular signals *** mechanism of uptake and the involvement of the cytoskeleton during the CS-NCs endocytosis variates among the different cell types as well as further effects observed inside *** the present work,we discuss the effects induced by CS-NCs per se on the cytoskeleton,a key component in cell architecture and *** focus of this report is made on tumoral and normal biological models in which CS-NCs could differentially affect the cell *** recent years reports regarding the impact of CS-NCs on cytoskeleton dynamics and the current techniques for its evaluation are summarized and *** mechanisms underlying cytoskeletal impact after cell exposure to CS-NCs is critical for the design of safest value-added formulations in the biomedical ***,this revision points out some interesting aspects of cytoskeletal changes and cell death encompassing anti-tumoral effects.

关键词： Cytoskeletal dynamics Cellular uptake Endocytosis Nanocarriers Chitosan Bioactive compounds

Analysis of the hydrological safety of dams combining two numerical tools:Iber and DualSPHysics

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Journal of Hydrodynamics 2018年第1期30卷 87-94页

作者： J.González-Cao O.García-Feal J.M.domínguez A.J.C.Crespo M.Gómez-Gesteira Environmental Physics Laboratory (EPHYSLAB) Universidade de Vigo Campus AsLagoas

The upgrade of the hydrological safety of dams is a critical issue to avoid failures that can dramatically affect people and assets. This paper shows a numerical methodology to analyse the safety of the Belesar dam（NW, Spain） based on two different numerical codes. First, a mesh-based code named Iber, suited to deal with large 2-D domains, is used to simulate the impoundment. The initial conditions and the inlet provided to Iber correspond to the maximum water elevation and the maximum expected inflow to the impoundment defined in the technical specifications of the dam, which are associated to the more hazardous operation conditions of the dam. Iber provides information about the time needed for water to attain the crest of the dam when floodgates are closed. In addition, it also provides the velocity of discharge when gates are opened. Then, a mesh-free code named DualSPHysics, which is especially suited to deal with complex and violent 3-D flows, is used to reproduce the behaviour of one of the spillways of the dam starting from the results obtained with Iber, which are used as inlet conditions for DualSPHysics. The combined results of both model show that the left spillway can discharge the surplus of water associated to the maximum inflow to the reservoir if the gates of the spillways are opened before the overtopping of the dam was observed. In addition, water depth measured on the spillway is considerably lower than the lateral walls, preventing overtopping. Finally, velocities at different points of the spillway showed to be in good agreement with theoretical values.

关键词： Hydrological safety dam numerical simulation Iber DualSPHysics

Usefulness of duodenal biopsy during routine upper gastrointestinal endoscopy for diagnosis of celiac disease

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World Journal of Gastroenterology 2006年第31期12卷 5028-5032页

作者： S Riestra F domínguez E Fernández-Ruiz E García-Riesco R Nieto E Fernández L Rodrigo Gastroenterology Section and Gastroenterology ServiceHospital Central de Asturias Spain Gastroenterology Section and Pathology ServiceHospital Valle del Nalón Spain Gastroenterology Section and Biochemistry ServiceHospital de Cabuenes Spain

AIM： To describe the trend in duodenal biopsy performance during routine upper gastrointestinal endoscopy in an adult Spanish population, and to analyze its value for the diagnosis of celiac disease in clinical practice. METHODS： A 15 year-trend （1990 to 2004） in duodenal biopsy performed when undertaking upper gastrointestinal endoscopy was studied. We analysed the prevalence of celiac disease in the overall group, and in the subgroups with anaemia and/or chronic diarrhoea. RESULTS： Duodenal biopsy was performed in 1033 of 13 678 upper gastrointestinal endoscopies （7.6%）; an increase in the use of such was observed over the study period （1.9% in 1990-1994, 5% in 1995-1999 and 12.8% in 2000-2004）. Celiac disease was diagnosed in 22 patients （2.2%）, this being more frequent in women than in men （3% and 1% respectively）. Fourteen out of 514 （2.7%） patients with anaemia, 12 out of 141 （8.5%） with chronic diarrhoea and 8 out of 42 （19%） with anaemia plus chronic diarrhoea had celiac disease. A classical clinical presentation was observed in 55% of the cases, 23% of the patients had associated dermatitis herpetiformis and 64% presented anaemia; 9% were diagnosed by familial screening and 5% by cryptogenetic hypertransaminasaemia. CONCLUSION： Duodenal biopsy undertaken during routine upper gastrointestinal endoscopy in adults, has been gradually incorporated into clinical practice, and is a useful tool for the diagnosis of celiac disease in high risk groups such as those with anaemia and/or chronic diarrhoea.

关键词： Duodenal biopsy Upper gastrointestinal endoscopy Celiac disease Anemia Chronic diarrhea

Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer’s disease

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Translational Neurodegeneration 2021年第3期10卷 487-501页

作者： Neus Barranco Virginia Plá Daniel Alcolea Irene Sánchez‑domínguez Reiner Fischer‑Colbrie Isidro Ferrer Alberto Lleó Fernando Aguado Department of Cell Biology Physiology and ImmunologyFaculty of BiologyUniversity of Barcelona08028 BarcelonaSpain Institute of Neurosciences University of Barcelona08028 BarcelonaSpain Memory Unit Department of NeurologySant Pau Biomedical Research Institute.Sant Pau HospitalAutonomous University of Barcelona08041 BarcelonaSpain Center for Net‑worked Biomedical Research on Neurodegenerative Diseases(CIBERNED) 28031 MadridSpain Department of Pharmacology Innsbruck Medical University6020 InnsbruckAustria Department of Pathology and Experi‑mental Therapeutics University of Barcelonaand Bellvitge University HospitalBellvitge Biomedical Research InstituteHospitalet de LlobregatSpain Pre‑sent Address:Center for Translational Neuromedicine University of Rochester Medical CenterRochesterNY 14642USA

Background:New fuid biomarkers for Alzheimer’s disease(AD)that reveal synaptic and neural network dysfunc‑tions are needed for clinical practice and therapeutic trial *** core vesicle(DCV)cargos are promising cerebrospinal fuid(CSF)indicators of synaptic failure in AD ***,their value as biomarkers has not yet been ***:Immunoassays were performed to analyze the secretory proteins prohormone convertases PC1/3 and PC2,carboxypeptidase E(CPE),secretogranins SgIII and SgII,and Cystatin C in the cerebral cortex(n=45,provided by Bellvitge University Hospital)and CSF samples(n=66,provided by The Sant Pau Initiative on Neurodegeneration cohort)from AD patients(n=56)and age-matched controls(n=55).Results:In AD tissues,most DCV proteins were aberrantly accumulated in dystrophic neurites and activated astro‑cytes,whereas PC1/3,PC2 and CPE were also specifcally accumulated in hippocampal granulovacuolar degeneration *** individuals displayed an overall decline of secretory proteins in the ***,in AD patients,the CSF levels of prohormone convertases strongly correlated inversely with those of neurodegeneration markers and directly with cognitive impairment ***:These results demonstrate marked alterations of neuronal-specifc prohormone convertases in CSF and cortical tissues of AD *** neuronal DCV cargos are biomarker candidates for synaptic dysfunction and neurodegeneration in AD.

关键词： Alzheimer’s disease Biomarkers Cerebral cortex Cerebrospinal fuid Granulovacuolar degeneration PCSK1 PCSK2 Tau protein

Device interchangeability on anterior chamber depth and white-to-white measurements: a thorough literature review

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International Journal of Ophthalmology(English edition) 2016年第7期9卷 1057-1065页

作者： Alberto domínguez-Vicent Cari Pérez-Vives Teresa Ferrer-Blasco Santiago García-Lázaro Robert Montés-Micó Optometry Research Group (GIO) Department of Optics and Optometry and Visual Science University of Valencia

We have reviewed a set of recently published studies that compared the anterior chamber depth（ACD） and/or white-to-white（WTW） distance obtained by means of different measuring *** some of those studies reached contradictory conclusions regarding device interchangeability,this review was carried out in attempting to clarify which clinical devices can or cannot be considered as interchangeable in clinical practice to measure ACD and/or WTW distance,among these devices：A-scan,ultrasound biomicroscopy,Orbscan and Orbscan Ⅱ（Bausch＆Lomb Surgical Inc.,San Dimas,California,USA）,Pentacam and Pentacam HR（Oculus,Wetzlar,Germany）,Galilei（Ziemer,Switzerland）,Visante optical coherence tomography（Visante OCT,Carl Zeiss Meditec Inc.,Dublin,California,USA）,lOLMaster（Carl Zeiss Meditec,Jena,Germany）,and Lenstar LS 900/Biograph（Haag-Streit AG,Koeniz,Switzerland/Alcon Laboratories Inc.,Ft Worth,Texas,USA）.

关键词： anterior camber depth measurement white to white measurement device interchangeability anterior chamber eye

Immunometabolism: A target for the comprehension of immune response toward transplantation

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World Journal of Transplantation 2019年第2期9卷 27-34页

作者： Omar domínguez-Amorocho Tatiana Takiishi Flavia Franco da Cunha Niels Olsen Saraiva Camara Department of Immunology Biomedical Sciences InstituteUniversity of Sao Paulo

Organ transplantation is a life-saving procedure, however predicting graft survival is still challenging. Understanding immune-cell pathobiology is critical to the development of effective therapies to prevent rejection. Over the recent years it has become progressively evident that the complex nature of immune cell behavioral dynamics is strongly dependent on cellular metabolism, which in turn, relies on competition for nutrients, oxygen and metabolites with other immune cells and microbiota. Furthermore, the influence of the inflammatory state can lead to substantial changes in conditions within the tissue microenvironment. Considering the context of immunity, alterations in metabolic pathways (glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway, the fatty acid oxidation and synthesis, and the amino acid metabolic pathways) will influence the production of different sets of cytokines and affect transplantation outcome. It is now known that na?ve, resting and effector cells acquire different metabolic profiles and studies have shown that specifically targeting some of these metabolic routes can prevent differentiation of effector T cells in favor of Tregs. Ultimately, to develop effective therapies that will prevent graft loss and understanding how cell metabolism impacts the fate and function of immune cells is now a critical point of discussion. The distinct metabolic features and requirements observed in effector and suppressive cell subsets offer promising opportunities for selective regulation of the immune responses in transplantation and will be discussed in this review.

关键词： Transplantation Metabolic processes Immune tolerance Metabolic activation Inflammatory response

Benzyl Amino Purine and Gibberellic Acid Coupled to Nitrogen-Limited Stress Induce Fatty Acids,Biomass Accumulation,and Gene Expression in Scenedesmus Obliquus

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Phyton-International Journal of Experimental Botany 2021年第2期90卷 515-531页

作者： Hans Christian Correa-Aguado Gloria Viviana Cerrillo-Rojas Alejandro Rocha-Uribe Ruth Elena Soria-Guerra JoséFrancisco Morales-domínguez Departamento de Química Centro de Ciencias BásicasUniversidad Autónoma de AguascalientesAguascalientes20131México Facultad de Ciencias Químicas Universidad Autónoma de San Luis PotosíSan Luis Potosí78210México Instituto Politécnico Nacional Unidad Profesional Interdisciplinaria de Ingeniería Campus ZacatecasBlvd.del Bote 202Cerro del Gato Ejido La EscondidaCol.Ciudad AdministrativaZacatecasZAC 98160Mexico

The need for renewable energy sources makes microalgae an essential feedstock for biofuels *** molecular aspects and the response to nitrogen(N)-limited conditions with a phytohormone stimulus in microalgae have been slightly *** this work,Scenedesmus obliquus was used as a study model to analyze the effect of benzyl amino purine(BAP)and gibberellic acid(GA)coupled to nitrogen limitation on cell growth,biomass and fatty *** selected 10^(-5)M BAP increased the biomass by 1.44-fold,and 10^(-6)M GA by *** total lipids also increased by 2.8 and 1.11-fold,*** 10^(-5)M BAP and 10^(-6)M GA addition to *** cultures at different initial nitrogen percentages(N-0,N-25,and N-50)showed a significant increase in cell growth and biomass productivity compared to the unstimulated *** N-0 and GA N-0 produced the highest lipid yields with 55%and 50%,*** lipid profile analysis revealed an increase,particularly in C18:1 and C16:0 fatty *** expression analysis showed an over-expression of acyl carrying protein(ACP),stearoyl-ACP desaturase(SAD),fatty acid acyl-ACP thioesterase(FATA),and diacylglycerol acyltransferase(DGAT)genes,which were mainly induced by nitrogen ***,BAP and GA produced a significant over-expression on these genes in the N-replete *** study shows that BAP and GA,coupled to N limitation stress,can be used to increase the biomass and lipid production in *** for sustainable biofuels.

关键词： Biodiesel gene expression lipids microalgae nitrogen deficiency phytohormones