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Effects of asymmetric dimethylarginine on renal arteries in portal hypertension and cirrhosis

World Journal of Gastroenterology 2016年第48期22卷 10545-10556页

作者： Gloria Segarra Belén Cortina maría dolores mauricio Susana Novella Paloma Lluch Javier Navarrete-Navarro Inmaculada Noguera Pascual Medina Department of Physiology University of Valencia and Institute of Health Research INCLIVAHospital Clínico Universitario Valencia Department of Gastroenterology and Hepatology and Institute of Health Research INCLIVA Hospital Clínico Universitario Valencia

AIM To evaluate the effects of asymmetric dimethylarginine(ADMA) in renal arteries from portal hypertensive and cirrhotic *** Rat renal arteries from Sham(n = 15), pre-hepatic portal hypertension(PPVL; n = 15) and bile duct ligation and excision-induced cirrhosis(BDL; n = 15) were precontracted with norepinephrine, and additional contractions were induced with ADMA(10-6-10-3 mol/L), an endogenous inhibitor of nitric oxide(NO) synthase. Concentration-response curves to acetylcholine(1 × 10-9^(-3) × 10^(-6) mol/L) were determined in precontractedrenal artery segments with norepinephrine in the absence and in the presence of ADMA. Kidneys were collected to determine the protein expression and activity of dimethylarginine dimethylaminohydrolase(DDAH), an enzyme that catabolizes ADMA. RESULTS In renal arteries precontracted with norepinephrine, ADMA caused endothelium-dependent contractions. The pD 2 values to ADMA were similar in the Sham and PPVL groups(4.20 ± 0.08 and 4.11 ± 0.09, P > 0.05, respectively), but were lower than those of the BDL group(4.79 ± 0.16, P < 0.05). Acetylcholine-induced endothelium-dependent relaxation that did not differ, in terms of p D2 and maximal relaxation, among the 3 groups studied. Treatment with ADMA(3 × 10^(-4) mol/L) inhibited acetylcholine-induced relaxation in the 3 groups, but the inhibition was higher(P < 0.05) in the BDL group compared with that for the Sham and PPVL groups. The m RNA and protein expression of DDAH-1 were similar in kidneys from the three groups. Conversely, DDAH-2 expression was increased(P < 0.05) in PPVL and further enhanced(P < 0.05) in the BDL group. However, renal DDAH activity was significantly decreased in the BDL group. CONCLUSION Cirrhosis increased the inhibitory effect of ADMA on basal- and induced-release of NO in renal arteries, and decreased DDAH activity in the kidney.

关键词： Portal hypertension Cirrhosis Nitric oxide Asymmetric dimethylarginine Nitric oxide inhibitors Dimethylarginine dimethylaminohydrolase

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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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Machine learning in liver surgery:Benefits and pitfalls

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World Journal of Clinical Cases 2024年第12期12卷 2134-2137页

作者： Rafael Calleja Manuel Durán maría dolores Ayllón Ruben Ciria Javier Briceño Hepatobiliary Surgery and Liver Transplantation Unit Hospital Universitario Reina SofíaMaimonides Biomedical Research Institute of CordobaCórdoba 14004Spain

The application of machine learning(ML)algorithms in various fields of hepatology is an issue of ***,we must be cautious with the *** this letter,based on a published ML prediction model for acute kidney injury after liver surgery,we discuss some limitations of ML models and how they may be addressed in the *** the future faces significant challenges,it also holds a great potential.

关键词： Machine learning Liver surgery Artificial intelligence Random forest Prediction model

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Phagocytosis: A Practical Approach for Evaluating Neutrophil Function in Health and Disease

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Modern Research in Inflammation 2024年第2期13卷 9-28页

作者： Oscar Rojas-Espinosa Patricia Arce-Paredes Sergio Islas-Trujillo Luis Enrique Becerril-Villanueva maría dolores Ponce-Regalado Departamento de Inmunologa Escuela Nacional de Ciencias Biolgicas Instituto Politcnico Nacional Ciudad de Mxico Mxico Laboratorio de Psicoinmunologa Instituto Nacional de Psiquiatra Ramn de la Fuente Ciudad de Mxico Mxico Departamento de Ciencias de la Salud Centro Universitario de los Altos Universidad de Guadalajara Jalisco Mxico

Neutrophils, crucial players in the effector phase of the immune response, are recognized as important mediators of both innate and adaptive immune responses. Through the production of pro- and anti-inflammatory cytokines, they modulate the function of T and other lymphoid cells. Countless reports have highlighted the importance of these cells as efficient antimicrobial agents and annotated their involvement in the pathology of infectious and noninfectious diseases. The development of modern, sophisticated technologies has allowed the study of the functions of these cells in clinical settings. These advanced technologies include fluorescence-activated cell sorters, confocal microscopy, automated cell image analyzers, and live cell analysis instruments. Unfortunately, the cost of these modern instruments, maintenance, reagents, and the need for qualified technicians prohibit their use in low-income laboratories and universities in developing countries. With this in mind, we propose a series of basic tests that can be used in low-input clinical laboratories and universities to evaluate the function of neutrophils in health and disease. Our methodology allows us to assess in a practical and low-cost manner the functions of neutrophils in the phagocytic process, including opsonization, ingestion, ROI production (NBT reduction), myeloperoxidase content, phagosome-lysosome fusion, microbicidal activity, and NET production. Thus, under a disadvantageous ambiance, this may guide physicians in deciding whether a patient’s illness involves phagocytic defects without imposing a heavy financial *** Abstract[-rId13-]

关键词： Phagocytosis Neutrophils Microbicidal Activity Netosis

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Vulvar Swelling in a 12-Year-Old Girl: An Early Manifestation of Crohn’s Disease

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Case Reports in Clinical Medicine 2024年第7期13卷 219-226页

作者： Stefania Rendina dolores Ferrara Rosanna Mamone Sara Isoldi Massimo Zeccolini Francesco Esposito Department of Radiology Universit degli studi di Napoli Luigi Vanvitelli Naples Italy Department of Radiology A.O.R.N. Santobono-Pausilipon Children Hospital Naples Italy Pediatric Gastroenterology and Hepatology Unit Santobono-Pausilipon Childrens Hospital Naples Italy

Vulvar Crohn’s disease (VCD) is a rare complication of Crohn’s disease, especially in pediatric population. An early diagnosis can result difficult if the complication does not present in conjunction with the classic gastrointestinal symptoms that characterize this disease. In this study we present the case of a 12-year-old girl whose initial symptom of Crohn’s disease was a symptomatic vulvar swelling promoted by a rectovaginal fistula. We also provide an overview of Crohn’s disease and the vulvar changes found in the course of this disease.

关键词： Recto-Vaginal Fistula Vulvar Swelling Metastatic Crohn’s Disease

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Functional traits:the pathways to riverine plant resistance in times of hydropeaking

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Ecological Processes 2023年第1期12卷 884-915页

作者： Alejandro Baladrón maría dolores Bejarano Isabel Boavida CERIS Civil Engineering Research and Innovation for SustainabilityInstituto Superior TécnicoUniversidade de LisboaAv.Rovisco Pais1049-001 LisbonPortugal Natural Resources Department Universidad Politécnica de Madrid(UPM)Calle JoséAntonio Novais1028040 MadridSpain

Hydropeaking,which refers to rising or falling discharges caused by the turning on or off of hydro-turbines to generate electricity,is a topic of growing interest due to its impact on fluvial *** date,most hydropeaking studies have focused on the impact of peak fluctuations on invertebrate and fish communities,but little attention has been paid to its impact on riverine plants and how functional traits may make them resistant to *** performed a review to assess how a set of 32 plant functional traits can be expressed in riverine plant species,and found evidence of how such expression affects their capacity to cope with common sources of hydropeaking disturbance(i.e.,inundation,fast water drawdown,and rapid water fluctuations linked to up-ramping and down-ramping hydropeaking operations).The information here presented can simplify the evaluation of impacts on riverine plant communities worldwide,as well as to detect suitable species to successfully restore rivers affected by hydropower production.

关键词： Drought Flooding Waterlogging Hydropeaking Plant trait Riverine vegetation

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Dendritic spine degeneration:a primary mechanism in the aging process

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Neural Regeneration Research 2025年第6期20卷 1696-1698页

作者： Gonzalo Flores Leonardo Aguilar-Hernández Fernado García-dolores Humberto Nicolini Andrea Judith Vázquez-Hernández Hiram Tendilla-Beltrán Instituto de Fisiología Benemérita Universidad Autónoma de Puebla(BUAP)PueblaMexico Instituto de Ciencias Forenses(INCIFO) Tribunal Superior de Justicia de la Ciudad de México(TSJCDMX).Mexico CityMexico Instituto Nacional de Medicina Genómica(INMEGEN) Mexico CityMexico

Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022;AguilarHernández et al., 2023).

关键词： aging process stress

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Characterization and QTL identification in eggplant introgression lines under two N fertilization levels

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Horticultural Plant Journal(园艺学报:英文版) 2023年第5期9卷 971-985页

作者： Elena Rosa-martínez Gloria Villanueva Ahmet Sahin Pietro Gramazio maría dolores García-martínez maría dolores Raig on Santiago Vilanova Jaime Prohens mariola Plazas Instituto de Conservacion y Mejora de la Agrodiversidad Valenciana Universitat Politecnica de ValenciaCamino de Vera 1446022 ValenciaSpain Instituto de Biología Molecular y Celular de Plantas Consejo Superior de Investigaciones Científicas-Universitat Politecnica de ValenciaCamino de Vera 1446022 ValenciaSpain

Lowering nitrogen inputs is a major goal for sustainable *** the present study,a set of 10 Solanum melongena introgression lines(ILs)developed using Solanum incanum as the exotic donor parent were grown under two nitrogen fertilization doses supplied with the irrigation system:1)8.25 mmol·L-1NH4NO3,corresponding to the high nitrogen treatment(HN),and 2)no external nitrogen supply,corresponding to the low nitrogen treatment(LN).Twenty traits,including plant growth and yield parameters,fruit size and morphology,nitrogen and carbon content in leaf and fruit,and phenolics content in fruit,were *** aim was to select of potential materials for eggplant breeding under low N inputs,as well as to identify and locate putative QTLs associated with the traits *** significant differences were observed between the soil characteristics of the HN and LN treatments,except for nitrogen and iron content,which was slightly lower in the HN,probably as a consequence of higher nutrient removal from soil by plants in the latter *** of variance showed that lowering nitrogen inputs did not significantly affect the final yield,fruit morphology,size and phenolics *** agronomic traits were highly and positively correlated with each other under both treatments,as well as total phenolics with chlorogenic acid *** assessment of the differences between each IL and the recipient parent resulted in the identification of 36 QTLs associated with most of the traits—12 were specific to the HN,17 specific to the LN,and 7 were stable across *** introgressed fragment of *** generally had a negative effect on the trait,except for QTLs for fruit dry matter,for fruit length on chromosome 10 under the HN,and for fruit pedicel length on chromosome 9 under the *** increase over AN-S-26 of the allele of *** for the QTLs detected ranged between-73.98% and 26.03% in HN and-73.67%and 34.43% in *** findings provide useful tools fo

关键词： Solanum melongena Solanum incanum Wild relatives N fertilization Abiotic stress QTL

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Alexander disease:the road ahead

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Neural Regeneration Research 2023年第10期18卷 2156-2160页

作者： maría A.Pajares Elena Hernández-Gerez Milos Pekny dolores Pérez-Sala Department of Structural and Chemical Biology Centro de Investigaciones Biológicas Margarita SalasMadridSpain Laboratory of Astrocyte Biology and CNS Regeneration Center for Brain RepairDepartment of Clinical NeuroscienceInstitute of Neuroscience and PhysiologySahlgrenska Academy at the University of GothenburgGothenburgSweden University of Newcastle NewcastleNSWand the Florey Institute of Neuroscience and Mental HealthParkvilleVICAustralia

Alexander disease is a rare neurodegenerative disorder caused by mutations in the glial fibrillary acidic protein,a type III intermediate filament protein expressed in *** early(infantile or juvenile)and adult onsets of the disease are known and,in both cases,astrocytes present characteristic aggregates,named Rosenthal *** are spread along the glial fibrillary acidic protein sequence disrupting the typical filament network in a dominant *** the presence of aggregates suggests a proteostasis problem of the mutant forms,this behavior is also observed when the expression of wild-type glial fibrillary acidic protein is ***,several isoforms of glial fibrillary acidic protein have been described to date,while the impact of the mutations on their expression and proportion has not been exhaustively ***,the posttranslational modification patterns and/or the protein-protein interaction networks of the glial fibrillary acidic protein mutants may be altered,leading to functional changes that may modify the morphology,positioning,and/or the function of several organelles,in turn,impairing astrocyte normal function and subsequently affecting *** particular,mitochondrial function,redox balance and susceptibility to oxidative stress may contribute to the derangement of glial fibrillary acidic protein mutant-expressing *** study the disease and to develop putative therapeutic strategies,several experimental models have been developed,a collection that is in constant *** fact that most cases of Alexander disease can be related to glial fibrillary acidic protein mutations,together with the availability of new and more relevant experimental models,holds promise for the design and assay of novel therapeutic strategies.

关键词： astrocytes endoplasmic reticulum stress glial fibrillary acidic protein mutants metabolism misassembly misfolding neurodegeneration oxidative stress posttranslational modifications unfolded protein response

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Angle-to-angle and spur-to-spur distance analysis with high-resolution optical coherence tomography

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Eye and Vision 2020年第1期7卷 399-411页

作者： Robert Montés-Micó Pedro Tañá-Rivero Salvador Aguilar-Córcoles maría Ruiz-Santos maría dolores Rodríguez-Carrillo Ramón Ruiz-Mesa Oftalvist Alicante and Jerez de la FronteraAlicanteSpain University of Valencia ValenciaSpain

Background:To measure angle-to-angle(ATA)and spur-to-spur(STS)distances along six meridians using highresolution swept-source optical coherence tomography(SS-OCT)and to compare those values with horizontal white-to-white(WTW)***:68 eyes from 68 patients were quantitatively assessed with the Anterion SS-OCT(Heidelberg Engineering,Heidelberg,Germany).ATA and STS distances were measured with the SS-OCT’s B-Scan in six cross-sectional images corresponding to the vertical(6-12 o’clock),1-7 o’clock,2-8 o’clock,horizontal(3-9 o’clock),4-10 o’clock and 5-11 o’clock *** was measured horizontally with the device’s infrared camera.A Pearson correlation analysis was carried out to compare ATA and STS distances with ***:The largest values were found for the vertical meridian and the shortest for the 2-8 o’clock meridian,both for ATA and STS *** statistically significant differences were found between WTW,ATA and STS along the horizontal meridian(p>0.1).However,ATA and STS showed statistically significant differences elsewhere,except for the horizontal and the 2-8 o’clock meridians(p>0.05).Moreover,we found that ATA and STS varied significantly depending on the meridian being assessed,except for ATA at 4-10 versus 3-9 o’clock and for STS at 4-10 versus 3-9 o’clock and at 3-9 versus 2-8 o’clock(p>0.1).R^(2) values ranged from 0.49 to 0.75 for ATA and STS at the different meridians,showing the best correlation at 3-9 o’clock meridian(0.64 and 0.75,respectively)and the worst at 6-12 o’clock meridian(R^(2)=0.49 for both ATA and STS).Conclusions:ATA and STS distances vary radially,thus showing that the anterior chamber is vertically ***,it is advisable to measure these two distances along the meridian to be used.

关键词： Angle-to-angle Spur-to-spur White-to-white Optical coherence tomography Swept-source Fourier domain

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