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Topical ocular administration of DPP-Ⅳ inhibitors:a new approach for treating diabetes-induced retinal neurodegeneration

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Neural Regeneration Research 2024年第4期19卷 713-714页

作者： Rafael Simó cristina hernández Diabetes and Metabolism Research Unit Vall d’Hebron Research Institute(VHIR) Department of Medicine Autonomous University of Barcelona Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas(CIBERDEM) Instituto de Salud CarlosⅢ(ICSⅢ)

Retinal neurodegeneration plays a significant role in the pathogenesis of diabetic retinopathy(DR),the leading cause of preventable *** fact,the American Diabetes Association has defined DR as a highly specific neurovascular complication(Solomon et al.,2017).Therefore,it is no longer acceptable to consider DR as merely a microvascular *** this regard,the term diabetic retinal disease(DRD)has been proposed as a broader term comprising microangiopathy and ***,there are currently no treatments available that directly target the neurodegenerative changes of *** paper will give new insights into the translational research in this field with particular emphasis on glucagon-like peptide 1/dipeptidyl peptidase IV(GLP-1/DPP-IV)inhibitors.

关键词： neurodegeneration ocular insight

Mechanisms of retinal neuroprotection of calcium dobesilate：therapeutic implications

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Neural Regeneration Research 2017年第10期12卷 1620-1622页

作者： Olga Simó-Servat cristina Solà-Adell Patricia Bogdanov cristina hernández Rafael Simó Diabetes and Metabolism Research Unit Vall d'Hebron Research InstituteCIBERDEM(Instituto de Salud CarlosⅢ)BarcelonaSpain

Current treatments for diabetic retinopathy （DR） are based on laser photocoagulation and intravitreal injections of corti- costeroids or anti-vascular endothelial growth factor （VEGF） agents. These treatments are applicable only at advanced stages of the disease. In addition, they are expensive, require a vitreo- retinal specialist and are associated with significant adverse ef- fects. Therefore, new pharmacological treatments for the early stages of the disease are needed.

关键词： Ca Mechanisms of retinal neuroprotection of calcium dobesilate:therapeutic implications

Using fused filament fabrication to improve the tribocorrosion behaviour of 17-4 PH SS in comparison to other metal forming techniques

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Friction 2024年第10期12卷 2325-2343页

作者： cristina GARCÍA-CABEZÓN Juan Alfonso NARANJO Celia GARCÍA-hernÁndez cristina BERGES Gemma HERRANZ Fernando MARTÍN-PEDROSA Materials Engineering E.I.I.Universidad de ValladolidValladolid 47011Spain INEI-Escuela Técnica Superior de Ingeniería Industrial(ETSII) Universidad de Castilla La ManchaCastilla-La Mancha 13071Spain

Fused filament fabrication(FFF)is one of the additive manufacturing processes which has gained more interest because of its simplicity and *** technology is similar to the conventional metal injection moulding(MIM)process,consisting of the feedstock preparation of metal powder and polymer binders,followed by layer-by-layer 3D printing(FFF)or injection(MIM)to create green parts and,finally,debinding and ***,both technologies provide near-dense *** work presents an in-depth study of the processing method’s *** porosity,microstructure,hardness,corrosion,and tribocorrosion behaviour are compared for 17-4 PH SS samples processed from powder by additive manufacturing using FFF and MIM,as well as conventional powder metallurgy(PM)*** samples exhibited the highest macro and microhardness,while corrosion behaviour was similar for both MIM and FFF samples,but superior in comparison to conventional PM ***,the FFF-as fabricated samples displayed a significant improvement in tribocorrosion resistance that could be explained by the higher proportion of delta ferrite and retained austenite in their microstructure.

关键词： 17-4 PH SS fused filament fabrication(FFF) metal injection moulding(MIM) corrosion behaviour powder metallurgy(PM) tribocorrosion behaviour

Effect of environmental enrichment on the body shape of the pumpkinseed

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Current Zoology 2020年第5期66卷 597-599页

作者： Noelle Fabre Anna vila-Gispert cristina Galobart Dolors Vinyoles Linguistic Education and Experimental/Mathematics Sciences Didactics Department Faculty of EducationUniversity of BarcelonaSpain GRECO Institute of Aquatic EcologyUniversity of GironaSpain Evolutionary Biology Ecology and Environmental Sciences DepartmentFaculty of BiologyUniversity of BarcelonaSpain

How the morphology of captive-reared fish is affected by structural enrichment in their rearing tanks is not well *** studies have suggested that deficiencies in rearing environments could produce inappropriate body shape in salmonids(Vehanen and Huusko 2011).Garduho-Paz et al.(2010)have found significant differences in body and head shapes of 3-spine stickleback Gasterosteus aculeatus,depending on whether fish were reared in an environment with just gravel or in an environment enriched with large stones and artificial plants.

关键词： shape pump body

Dendritic nanoarchitecture imparts ZSM-5 zeolite with enhanced adsorption and catalytic performance in energy applications

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Journal of Energy Chemistry 2023年第5期80卷 77-88,I0003页

作者： María del Mar Alonso-Doncel cristina Ochoa-hernández Gema Gómez-Pozuelo Adriana Oliveira JoséGonzález-Aguilar ángel Peral Raúl Sanz David P.Serrano Thermochemical Processes Unit IMDEA Energy InstituteAvda.Ramon de la Sagra3E28935MostolesMadridSpain Department of Heterogeneous Catalysis Max-Planck-Institut für KohlenforschungKaiser-Wilhem-Platz14540Muheim an der RuhGermay Department of Chemical and Environmental Technology Rey Juan Carlos UniversityC/Tulipan s/nE28933MostolesMadridSpain High Temperature Processes Unit IMDEA Energy InstituteAvda.Ramon de la Sagra3E28935MostolesMadridSpain Department of Chemical Energy and Mechanical TechnologyRey Juan Carlos UniversityC/Tulipan s/n28933MostolesMadridSpain

The development of zeolites possessing dendritic features represents a great opportunity for the design of novel materials with applications in a large variety of fields and,in particular,in the energy sector to afford its transition towards a low carbon *** the current work,ZSM-5 zeolite showing a dendritic3D nanoarchitecture has been synthesized by the functionalization of protozeolitic nanounits with an amphiphilic organosilane,which provokes the branched aggregative growth of zeolite *** ZSM-5 exhibits outstanding accessibility arising from a highly interconnected network of radially-oriented mesopores(3-10 nm)and large cavities(20-80 nm),which add to the zeolitic micropores,thus showing a well-defined trimodal pore size *** singular features provide dendritic ZSM-5 with sharply enhanced performance in comparison with nano-and hierarchical reference materials when tested in a number of energy related applications,such as VOCs(toluene)adsorption(improved capacity),plastics(low-density polyethylene)catalytic cracking(boosted activity)and hydrogen production by methane catalytic decomposition(higher activity and deactivation resistance).

关键词： Dendritic ZSM-5 VOCs adsorption Plastics cracking Methane decomposition Hydrogen production

C3G contributes to platelet activation and aggregation by regulating major signaling pathways

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2103-2117页

作者： Sara Gutiérrez-Herrero cristina Fernández-Infante Luis hernández-Cano Sara Ortiz-Rivero Carlos Guijas Víctor Martín-Granado JoséRamón González-Porras Jesús Balsinde Almudena Porras Carmen Guerrero Instituto de Biología Molecular y Celular del Cáncer(IMBCC) University of Salamanca-CSICSalamancaSpain Instituto de Investigación Biomédica de Salamanca(IBSAL) SalamancaSpain Instituto de Biología y Genética Molecular(IBGM) Consejo Superior de Investigaciones Científicas(CSIC)University of ValladolidValladolidSpain Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas(CIBERDEM) MadridSpain Departamento de Hematologiá Hospital Universitario de Salamanca(HUS)SalamancaSpain Departamento de Bioquímica y Biología Molecular Facultad de FarmaciaComplutense University of Madrid.Instituto de Investigación Sanitaria del Hospital Clínico San Carlos(IdISSC)MadridSpain Departamento de Medicina University of SalamancaSalamancaSpain

C3G is a GEF(guanine nucleotide exchange factor)for Rap GTPases,among which the isoform Rap1b is an essential protein in platelet *** transgenic mouse models with platelet-specific overexpression of C3G or mutant C3GΔCat,we have unveiled a new function of C3G in regulating the hemostatic function of platelets through its participation in the thrombin-PKCRap1b pathway.C3G also plays important roles in angiogenesis,tumor growth,and metastasis through its regulation of the platelet *** addition,C3G contributes to megakaryopoiesis and ***,we used a platelet-specific C3G-KO mouse model to further support the role of C3G in hemostasis.C3G-KO platelets showed a significant delay in platelet activation and aggregation as a consequence of the defective activation of Rap1,which resulted in decreased thrombus formation in ***,we explored the contribution of C3G-Rap1b to platelet signaling pathways triggered by thrombin,PMA or ADP,in the referenced transgenic mouse model,through the use of a battery of specific *** found that platelet C3G is phosphorylated at Tyr504 by a mechanism involving *** phosphorylation was shown to be positively regulated by ERKs through their inhibition of the tyrosine phosphatase ***,C3G participates in the ADP-P2Y12-PI3K-Rap1b pathway and is a mediator of thrombin-TXA2 ***,it inhibits the synthesis of TXA2 through cPLA2 *** together,our data reveal the critical role of C3G in the main pathways leading to platelet activation and aggregation through the regulation of Rap1b.

关键词： C3G platelet activation

What can we learn from β-cell failure biomarker application in diabetes in childhood?A systematic review

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World Journal of Diabetes 2021年第8期12卷 1325-1362页

作者： María F Calderón-hernández Nelly F Altamirano-Bustamante cristina Revilla-Monsalve María Belen Mosquera-Andrade Myriam M Altamirano-Bustamante Unidad de Investigación en Enfermedades Metabólicas Centro Médico Nacional Siglo XXIIMSSMexico 06720Mexico Department of Endocrinology Instituto Nacional de PediatríaMexico 04530Mexico

BACKGROUND The prevalence of diabetes as a catastrophic disease in childhood is growing in the *** search for novel biomarkers ofβ-cell failure has been an elusive task because it requires several clinical and biochemical measurements in order to integrate the risk of metabolic *** To determine which biomarkers are currently used to identifyβ-cell failure among children and adolescents with high risk factors for diabetes *** This systematic review was carried out using a modified version of the PICO protocol(Participants/Intervention/Comparison/Outcome).Once our research question was established,terms were individually researched on three different databases(PubMed,BIREME and Web of Science).The total articles obtained underwent a selection process from which the 78 most relevant articles were retrieved to undergo further *** were assessed individually according to quality *** First,we made the classification of theβ-cell-failure biomarkers by the target tissue and the evolution of the disease,separating the biomarkers in relation to the types of ***,we demonstrated that most biomarkers currently used as early signs ofβ-cell failure are those that concern local or systemic inflammation processes and oxidative stress as well as those related to endothelial dysfunction ***,we explored the novelties of diabetes as a protein conformational disease and the novel biomarker called real human islet amyloid polypeptide amyloid ***,we ended with a discussion about the best practice of validation and individual control of using different types of biomarkers in type 1 and type 2 diabetes in order to assess the role they play in the progress of diabetes in *** This review makes widely evident that most biomarkers currently used as early signs ofβ-cell failure are those that concern local or systemic inflammation processes and oxidative stress as well as those related to endo

关键词： Biomarker β-cell failure Children Adolescents Diabetes mellitus Metabolic syndrome

Neurodegeneration:An early event of diabetic retinopathy

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World Journal of Diabetes 2010年第2期1卷 57-64页

作者： Marta Villarroel Andreea Ciudin cristina hernández Rafael Simó Diabetes and Metabolism Research Unit.Institut de Recerca Hospital Universitari Vall D'Hebron Universitat Autònoma de Barcelona CIBER for Diabetes and Associated Metabolic Diseases(CIBERDEM Instituto de Salut CarlosⅢ)

Diabetic retinopathy(DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by ***,retinal neurodegeneration is already present before any microcirculatory abnormalities can be detected in ophthalmoscopic *** other words,retinal neurodegeneration is an early event in the pathogenesis of DR which predates and participates in the microcirculatory abnormalities that occur in ***,the study of the mechanisms that lead to neurodegeneration will be essential to identify new therapeutic targets in the early stages of *** levels of glutamate and the overexpression of the renin-angiotensin-system play an essential role in the neurodegenerative process that occurs in diabetic *** neuroprotective factors,pigment epithelial derived factor,somatostatin and erythropoietin seem to be the most relevant and these will be considered in this ***,it should be noted that the balance between neurotoxic and neuroprotective factors rather than levels of neurotoxic factors alone will determine the presence or absence of retinal neurodegeneration in the diabetic *** strategies,based on either the delivery of neuroprotective agents or the blockade of neurotoxic factors,are currently being tested in experimental models and in clinical pilot *** these novel therapies will eventually supplement or prevent the need for laser photocoagulation or vitrectomy awaits the results of additional clinical research.

关键词： Diabetic retinopathy Angiotensin II Erythropoietin Glutamate Retinal neurodegeneration Neuropeptides Pigment epithelial derived factor Somatostatin

Distribution of DNA damage in the human sperm nucleus:implications of the architecture of the sperm head

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Asian Journal of Andrology 2020年第4期22卷 401-408页

作者： Silvia González-Rojo cristina Fernández-Díez Marta Lombó María Paz Herráez Department of Molecular Biology Faculty of BiologyUniversidad de LeónCampus de Vegazana s/n LeónLeón 24071Spain

The sperm nucleus is prone to sustain DNA damage before and after *** of the damage is not homogeneous,and the factors determining differential sensitivity among nuclear regions have not yet been *** sperm chromatin contains three structural domains,two of which are considered the most susceptible to DNA damage:the histone bound domain,harboring developmental related genes,and the domain associated with nuclear matrix *** a quantitative polymerase chain reaction(qPCR)approach,we analyzed the number of lesions in genes homeobox A3(HOXA3),homeobox B5(HOXB 5),sex-determining region Y(SRY)-box 2(SOX2),β-GLOBIN,rDNA 18S,and rDNA 28S in human sperm after ultraviolet irradiation(400μW cm−2,10 min),H2O2treatment(250 mmol l−1,20 min),and cryopreservation,which showed differential susceptibility to genetic *** vulnerability is dependent on the genotoxic agent and independent of the sperm nuclear proteins to which the chromatin is bound and of accessibility to the transcription *** of 8-hydroxy-2'-deoxyguanosine(8-OHdG)showed that the highest level of oxidation was observed after *** distribution of oxidative lesions also differed depending on the genotoxic agent.8-OHdG did not colocalize either with histone 3(H3)or with type IIα+βtopoisomerase(TOPO IIα+β)after H2O2treatment but matched perfectly with peroxiredoxin 6(PRDX6),which is involved in *** study reveals that the characteristics of the sperm head domains are responsible for access of the genotoxicants and cause differential degree of damage to nuclear areas,whereas chromatin packaging has a very limited *** histone-enriched genes analyzed cannot be used as biomarkers of oxidative DNA damage.

关键词： biomarkers DNA damage human sperm oxidative stress sperm chromatin sperm quality