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Pembrolizumab autoimmune related diabetes:Moving forward,keep learning

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World Journal of Clinical Oncology 2024年第5期15卷 576-579页

作者： Jose Angel garcia Diego Alcaraz esther Holgado Felipe Couñago Department of Medical Oncology GenesisCare Spain-San Francisco de Asis University HospitalMadrid 28002Spain Department of Chief of Medical Oncology GenesisCare Spain-San Francisco de Asis University HospitalMadrid 28002Spain Department of Chief of Radiation Oncology GenesisCare-Vithas La Milagrosa HospitalMadrid 28010Spain

Immune checkpoint inhibitors(and more specifically programmed cell death 1/programmed cell death ligand 1 inhibitors as Pembrolizumab)initiated a revolution in the field of melanoma and have now expanded to several tumor subtypes and in increasingly broader clinical contexts,including the adjuvant and neoadjuvant setting,with potentially curable patients and prolonged *** side effects related to these drugs include a wide spectrum of manifestations,with endocrinological adverse events being some of the most ***-induced type 1 diabetes mellitus is an infrequent but potentially serious and not clearly reversible side effect that possesses characteristic clinical features and has high morbidity and mortality,with a chronic impact on quality of *** etiopathogenesis of this phenomenom needs to be further investigated and a collaborative effort through the involvement of oncologists and other medical specialists is necessary for the correct identification and management of patients at risk.

关键词： Immune checkpoints Pembrolizumab Immunotherapy Side effects Endocrine system Diabetes mellitus

Effect of Mushroom Extract Hericium erinaceus on Spatial Memory and Morphology of Neurons in the CA1 and CA3 Regions of the Hippocampus in Ovariectomized Rats

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Open Journal of Veterinary Medicine 2024年第7期14卷 163-179页

作者： Lucia garcia-Delgado Mariana Monserrath Verdía-Venegas Jacinto Bañuelos-Pineda esther Albarrán-Rodríguez Guillermo Nolasco-Rodriguez José Ricardo Cuellar-Pérez Sergio Fausto-Guerra Manuel Rosales-Cortés Master in Behavioral Sciences Institute of Neurosciences University of Guadalajara Zapopan Mexico Department of Veterinary Medicine Division of Veterinary Sciences CUCBA University of Guadalajara Zapopan Mexico Botany and Zoology Laboratory CUCBA University of Guadalajara Zapopan Mexico

Various studies indicate that low levels of estradiol negatively impact cognitive abilities. Extracts from the fungus Hericium erinaceus (HE) contain bioactive components that promote the proper functioning of the nervous system and potential effects on protection against neurodegenerative diseases, including dementia and motor dysfunctions. The objective was to evaluate the effects of the administration of the HE mushroom extract on visuospatial memory and morphology of neurons in the CA1 and CA3 regions of the hippocampus in ovariectomized rats. 40 young Wistar rats weighing 90 ± 10 g BW were used, which were distributed into four groups of 10 animals;Control Group, non-ovariectomized and untreated rats;Group E2, ovariectomized rats treated with estradiol (2 μg/kg/body weight);Group HE, ovariectomized rats treated with the extract of the fungus Hericium erinaceus (0.5 mg/kg body weight) and Group Ovx/ST, ovariectomized rats, without treatment. The animals were tested in the Barnes and Open Field maze, then they were sacrificed, and their brains were obtained to perform a histological analysis of neuronal morphology in the CA1 and CA3 areas of the hippocampus. The most outstanding results showed that the Ovx/ST group recorded the longest time to arrive at the escape box and stay in the Barnes maze. A correlation was observed between neuronal damage and function;in the groups that did not present satisfactory performance in the maze tests, morphological alterations were identified such as the presence of some neuronal somata with degeneration characteristics such as pyknosis, nuclear basophilia and shrinkage of the cells. Its soma, as well as a decrease in the nuclear area of CA1 and CA3 neurons. It is concluded that the fungus Hericium erinaceus exerted a neuroprotective effect on the neuronal bodies of the hippocampus, associated with better performance in the visuospatial recognition memory test.

关键词： Ovariectomized Rats Ovarian Hypofunction Estradiol Hericium erinaceus Barnes Circular Labyrinth Open Field Labyrinth

DET1-mediated COP1 regulation avoids HY5 activity over second-site gene targets to tune plant photomorphogenesis

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Molecular Plant 2021年第6期14卷 963-982页

作者： esther Canibano Clara Bourbousse Marta garcia-Leon Borja Garnelo Gomez Lea Wolff Camila garcia-Baudino Rosa Lozano-duran Fredy Barneche Vicente Rubio Sandra Fonseca Centro Nacional de Biotecnología CNB-CSICMadrid 28049Spain Institut de biologie de l’École normale supérieure(IBENS) École normale supérieureCNRSINSERMUniversitéPSLParis 75005France Shanghai Center for Plant Stress Biology CAS Center for Excellence in Molecular Plant SciencesChinese Academy of SciencesShanghai 201602China Department of Plant Biochemistry Centre for Plant Molecular Biology(ZMBP)Eberhard Karls University72076 TübingenGermany

DE-ETIOLATED 1(DET1)and CONSTITUTIVE PHOTOMORPHOGENESIS 1(COP1)are two essential repressors of Arabidopsis *** proteins can associate with CULLIN4 to form independent CRL4-based E3 ubiquitin ligases that mediate the degradation of several photomorphogenic transcription factors,including ELONGATED HYPOCOTYL 5(HY5),thereby controlling multiple gene-regulatory *** extensive biochemical and genetic analyses of their multi-subunit complexes,the functional links between DET1 and COP1 have long remained ***,we report that DET1 associates with COP1 in vivo,enhances COP1-HY5 interaction,and promotes COP1 destabilization in a process that dampens HY5 protein *** regulating its accumulation,DET1 avoids HY5 association with hundreds of second-site genomic loci,which are also frequently targeted by the skotomorphogenic transcription factor PHYTOCHROME-INTERACTING FACTOR ***,ectopic HY5 chromatin enrichment favors local gene repression and can trigger fusca-like *** study therefore shows that DET1-mediated regulation of COP1 stability tunes down the HY5 cistrome,avoiding hyper-photomorphogenic responses that might compromise plant viability.

关键词： HY5 DET1 COP1 photomorphogenesis light signaling fusca

Understanding the immune response and the current landscape of immunotherapy in pancreatic cancer

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World Journal of Gastroenterology 2021年第40期27卷 6775-6793页

作者： Lorena Ostios-garcia Julia Villamayor esther garcia-Lorenzo David Vinal Jaime Feliu Department of Oncology La Paz University HospitalIDIPAZCIBERONCCátedra UAMAMGENMadrid 28046Spain

Pancreatic ductal adenocarcinoma(PDAC)is an aggressive tumor with high *** with surgery,radiotherapy,chemotherapy,and other locoregional or systemic therapies,the survival rates for PDAC are low and have not significantly changed in the past *** special characteristics of the PDAC’s microenvironment and its complex immune escape mechanism need to be considered when designing novel therapeutic approaches in this *** is characterized by chronic inflammation with a high rate of tumor-associated macrophages and myeloid-derived suppressor cells and a low rate of natural killer and effector T *** pancreatic microenvironment is a fibrotic,microvascularized stroma that isolates the tumor from systemic ***,a novel approach that has demonstrated effectiveness in certain solid tumors,has failed to show any practice-changing results in pancreatic cancer,with the exception of PDACs with mismatch repair deficiency and high tumor mutational burden,which show prolonged survival rates with ***,numerous clinical trials are attempting to assess the efficacy of immunotherapeutic strategies in PDAC,including immune checkpoint inhibitors,cancer vaccines,and adoptive cell transfer,alone or in combination with other immunotherapeutic agents,chemoradiotherapy,and other targeted therapies.A deep understanding of the immune response will help in the development of new therapeutic strategies leading to improved clinical outcomes for patients with PDAC.

关键词： Pancreatic cancer Immunity Immune evasion Tumor microenvironment Immunotherapy Cancer vaccines

Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering

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Science China Materials 2020年第1期63卷 147-156页

作者： Eric Volta-duran Olivia Cano-Garrido Naroa Serna Hector Lopez-Laguna Laura Sanchez-garcia Mireia Pesarrodona Alejandro Sanchez-Chardi Ramon Mangues Antonio Villaverde esther Vazquez Ugutz Unzueta Institut de Biotecnologia i de Biomedicina Universitat Autònoma de BarcelonaBellaterra08193 BarcelonaSpain Departament de Genetica i de Microbiologia Universitat Autònoma de BarcelonaBellaterra08193 BarcelonaSpain CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN)C/Monforte de Lemos 3-528029 MadridSpain Nanoligent SL Edifici EUREKAUniversitat Autonoma de BarcelonaBellaterra08193 BarcelonaSpain Institut dInvestigacions Biomèdiques Sant Pau and Josep Carreras Research Institute Hospital de la Santa Creu i Sant Pau08041 BarcelonaSpain Departament de Biologia Evolutiva Ecologia i Ciencies AmbientalsFacultat de BiologiaUniversitat de BarcelonaAv.Diagonal 64308028 BarcelonaSpain Institute for Research in Biomedicine(IRB Barcelona) The Barcelona Institute of Science and Technology08028 BarcelonaSpain

Modular protein engineering is suited to recruit complex and multiple functionalities in single-chain polypeptides. Although still unexplored in a systematic way, it is anticipated that the positioning of functional domains would impact and refine these activities, including the ability to organize as supramolecular entities and to generate multifunctional protein materials. To explore this concept, we have repositioned functional segments in the modular protein T22-GFP-H6 and characterized the resulting alternative fusions. In T22-GFP-H6, the combination of T22 and H6 promotes selfassembling as regular nanoparticles and selective binding and internalization of this material in CXCR4-overexpressing tumor cells, making them appealing as vehicles for selective drug delivery. The results show that the pleiotropic activities are dramatically affected in module-swapped constructs, proving the need of a carboxy terminal positioning of H6 for protein self-assembling, and the accommodation of T22 at the amino terminus as a requisite for CXCR4^+ cell binding and internalization. Furthermore, the failure of self-assembling as regular oligomers reduces cellular penetrability of the fusions while keeping the specificity of the T22-CXCR4 *** these data instruct how multifunctional nanoscale protein carriers can be designed for smart, protein-driven drug delivery, not only for the treatment of CXCR4^+ human neoplasias, but also for the development of anti-HIV drugs and other pathologies in which CXCR4 is a relevant homing marker.

关键词： nanoparticles protein materials recombinant proteins drug delivery self-assembling cancer cell targeting

Understanding bottom-up continuous hydrothermal synthesis of nanoparticles using empirical measurement and computational simulation

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Nano Research 2016年第11期9卷 3377-3387页

作者： Jose Sierra-Pallarest Thomas Huddle Juan garcia-Serna esther Alonso Fidel Mato Igor Shvets Olaf Luebben Maria Jose Cocero Edward Lester Fluids Engineering Group Energy and Fluid Mechanics Engineering Department University of Valladolid Paseo del Cauce 59 47010 Valladolid Spain Advanced Materials Research Group the University of Nottingham University Park Nottingham NG7 2RD UK High Pressure Processes Group Department of Chemical Engineering and Environmental Technology University of Valladolid C/Prado de la Magdalena s/n 47011 Valladolid Spain School of Physics Trinity College Dublin College green Dublin 2 Ireland

Continuous hydrothermal synthesis was highlighted in a recent review as an enabling technology for the production of nanoparticles. In recent years, it has been shown to be a suitable reaction medium for the synthesis of a wide range of nanomaterials. Many single and complex nanomaterials such as metals, metal oxides, doped oxides, carbonates, sulfides, hydroxides, phosphates, and metal organic frameworks can be formed using continuous hydrothermal synthesis techniques. This work presents a methodology to characterize continuous hydrothermal flow systems both experimentally and numerically, and to determine the scalability of a counter current supercritical water reactor for the large scale production （〉1,000 T-year-1） of nanomaterials. Experiments were performed using a purpose-built continuous flow rig, featuring an injection loop on a metal salt feed line, which allowed the injection of a chromophoric tracer. At the system outlet, the tracer was detected using UV/Vis absorption, which could be used to measure the residence time distribution within the reactor volume. Computational fluid dynamics （CFD） calculations were also conducted using a modeled geometry to represent the experimental apparatus. The performance of the CFD model was tested against experimental data, verifying that the CFD model accurately predicted the nucleation and growth of the nanomaterials inside the reactor.

关键词： nanoparticle computational fluid dynamics synthesis supercritical inorganics

Exploiting the diversity of tomato:the development of a phenotypically and genetically detailed germplasm collection

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Horticulture Research 2020年第1期7卷 1941-1954页

作者： Estefanía Mata-Nicolás Javier Montero-Pau esther Gimeno-Paez Víctor garcia-Carpintero Peio Ziarsolo Naama Menda Lukas A.Mueller JoséBlanca Joaquín Cañizares esther van der Knaap María JoséDíez Instituto Universitario de Conservación y Mejora de la Agrodiversidad Valenciana.COMAV.Universitat Politècnica de València ValenciaSpain Department of Biochemistry and Molecular Biology Universitat de ValènciaValenciaSpain Boyce Thompson Institute IthacaNYUSA Institute of Plant Breeding Genetics and GenomicsUniversity of GeorgiaGeorgiaGAUSA Department of Horticulture University of GeorgiaGeorgiaGAUSA

A collection of 163 accessions,including Solanum pimpinellifolium,Solanum lycopersicum *** and Solanum lycopersicum ***,was selected to represent the genetic and morphological variability of tomato at its centers of origin and domestication:Andean regions of Peru and Ecuador and *** collection is enriched with *** *** from the Amazonian region that has not been analyzed previously nor used *** collection has been morphologically characterized showing diversity for fruit,flower and vegetative *** genomes were sequenced in the Varitome project and are publicly available(***/projects/varitome).The identified SNPs have been annotated with respect to their impact and a total number of 37,974 out of 19,364,146 SNPs have been described as high impact by the SnpEeff *** has shown associations for different traits,demonstrating the potential of this collection for this kind of *** have not only identified known QTLs and genes,but also new regions associated with traits such as fruit color,number of flowers per inflorescence or inflorescence *** speed up and facilitate the use of this information,F2 populations were constructed by crossing the whole collection with three different *** F2 collection is useful for testing SNPs identified by GWAs,selection sweeps or any other candidate *** data is available on Solanaceae Genomics Network and the accession and F2 seeds are freely available at COMAV and at TGRC *** these resources together make this collection a good candidate for genetic studies.

关键词： germplasm collection traits

Comparison between type-2 and type-1 myocardial infarction：clinical features, treatment strategies and outcomes

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Journal of Geriatric Cardiology 2016年第1期13卷 15-22页

作者： Angel Lopez-Cuenca Miriam Gomez-Molina Pedro J Flores-Blanco Marianela Sanchez-Martinez Andrea garcia-Narbon Ignacio De Las Heras-Gomez Maria J Sainchez-Galian esther Guerrero-Perez Mariano Valdes Sergio Manzano-Femandez Department of Internal Medicine Hospital de la Vega Lorenzo Guirao Cieza Spain Division of Cardiology University Hospital Virgen de la Arrixaca School of Medicine IMIB Murcia Spain Department of Biochemistry University Hospital Virgen de la Arrixaca School of Medicine IMIB Murcia Spain Department of lnternal Medicine University of Murcia Murcia Spain

Objective To assess the differences in incidence, clinical features, current treatment strategies and outcome in patients with type-2vs. type-1 acute myocardial infarction （AMI）.Methods We included 824 consecutive patients with a diagnosis of type-1 or type-2 AMI. Dur-ing index hospitalization, clinical features and treatment strategies were collected in detail. At 1-year follow-up, mortality, stroke, non-fatal myocardial infarction and major bleeding were ***-1 AMI was present in 707 （86%） of the cases while 117 （14%） were classified as type-2. Patients with type-2 AMI were more frequently female and had higher co-morbidities such as diabetes, previous non-ST segment elevation acute coronary syndromes, impaired renal function, anaemia, atrial fibrillation and malignancy. However, preserved left ventricular ejection fraction and normal coronary arteries were more frequently seen, an invasive treatment was less common, and anti-platelet medications, statins and beta-blockers were less prescribed in patients with type-2 AMI. At 1-year follow-up, type-2 AMI was associated with a higher crude mortality risk （HR： 1.75, 95% CI： 1.14-2.68;P = 0.001）, but this association did not remain significant after multivariable adjustment （P = 0.785）. Furthermore, we did not find type-2 AMI to be associated with other clinical *** In this real-life population, compared with type-1, type-2 AMI were predominantly women and had more co-morbidities. Invasive treatment strategies and cardioprotective medications were less used in type-2, while the 1-year clinical outcomes were similar.

关键词： Coronary vessels Follow-up studies Myocardial infarction

Physical exercise in the prevention and treatment of Alzheimer’s disease

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Journal of Sport and Health Science 2020年第5期9卷 394-404页

作者： Adrian De la Rosa Gloria Olaso-Gonzalez Coralie Arc-Chagnaud Fernando Millan Andrea Salvador-Pascual Consolacion Garcıa-Lucerga Cristina Blasco-Lafarga esther garcia-Dominguez Aitor Carretero Angela G.Correas Jose Vina Mari Carmen Gomez-Cabrera Freshage Research Group Department of PhysiologyFaculty of MedicineUniversity of Valenciaand CIBERFESInsitute of Health Research-INCLIVAValencia 46010Spain INRA UMR866 Muscle dynamics and metabolismUniversity of MontpellierF-34060MontpellierFrance Department of Physiotherapy Faculty of PhysiotherapyUniversity of ValenciaValencia 46010Spain Physical Education and Sports Department University of ValenciaValencia 46010Spain

Dementia is one of the greatest global challenges for health and social care in the 21st ***’s disease(AD),the most common type of dementia,is by no means an inevitable consequence of growing *** lifestyle factors may increase,or reduce,an individual’s risk of developing *** has been written over the ages about the benefits of exercise and physical *** the risk factors associated with AD is a low level of physical *** relationship between physical and mental health was established several years *** this review,we discuss the role of exercise(aerobic and resistance)training as a therapeutic strategy for the treatment and prevention of *** adults who exercise are more likely to maintain *** address the main protective mechanism on brain function modulated by physical exercise by examining both human and animal *** will pay especial attention to the potential role of exercise in the modulation of amyloid b turnover,inflammation,synthesis and release of neurotrophins,and improvements in cerebral blood *** changes in lifestyle in presymptomatic and predementia disease stages may have the potential for delaying one-third of dementias *** interventions that include the adoption of an active lifestyle should be recommended for older populations.

关键词： Aerobic exercise Dementia Exercise training Lifestyle factors Multidomain interventions Resistance exercise