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Precision medicine in pantothenate kinase-associated neurodegeneration

Neural Regeneration Research 2019年第7期14卷 1177-1185页

作者： mónica álvarez-Córdoba marina Villanueva-Paz Irene Villalón-García Suleva Povea-Cabello Juan m.Suárez-Rivero marta Talaverón-Rey Javier Abril-Jaramillo ana Belén Vintimilla-Tosi José A.Sánchez-Alcázar Centro Andaluz de Biología del Desarrollo(CABD-CSIC-Universidad Pablo de Olavide) and Centro de Investigación Biomédica en Red:Enfermedades RarasInstituto de Salud Carlos Ⅲ Centro de Neurología Avanzada Centro Civet

Neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas,mainly the basal *** predominant clinical symptoms include spasticity,progressive dystonia,Parkinson's disease-like symptoms,neuropsychiatric alterations,and retinal *** the neurodegeneration with brain iron accumulation disorders,the most frequent subtype is pantothenate kinase-associated neurodegeneration(PKAN) caused by defects in the gene encoding the enzyme pantothenate kinase 2(PANK2)which catalyzed the first reaction of the coenzyme A biosynthesis *** there is no effective treatment to prevent the inexorable course of these *** aim of this review is to open up a discussion on the utility of using cellular models derived from patients as a valuable tool for the development of precision medicine in ***,we have described that dermal fibroblasts obtained from PKAN patients can manifest the main pathological changes of the disease such as intracellular iron accumulation accompanied by large amounts of lipofuscin granules,mitochondrial dysfunction and a pronounced increase of markers of oxidative *** addition,PKAN fibroblasts showed a morphological senescence-like ***,pantothenate supplementation,the substrate of the PANK2 enzyme,corrected all pathophysiological alterations in responder PKAN fibroblasts with low/residual PANK2 enzyme ***,pantothenate treatment had no favourable effect on PKAN fibroblasts harbouring mutations associated with the expression of a truncated/incomplete *** correction of pathological alterations by pantothenate in individual mutations was also verified in induced neurons obtained by direct reprograming of PKAN *** observations indicate that pantothenate supplementation can increase/stabilize the expression levels of PANK2 in s

关键词： neurodegeneration with brain iron accumulation pantothenate kinase-associated neurodegeneration pantothenate kinase 2 pantothenate induced neurons precision medicine induced neuron fibroblast

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Insights into the swelling process and drug release mechanisms from cross-linked pectin/high amylose starch matrices

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Asian Journal of Pharmaceutical Sciences 2014年第1期9卷 27-34页

作者： Fernanda m.Carbinatto ana Do´ris de Castro Raul C.Evangelista Beatriz S.F.Cury Graduate Program in Pharmaceutical Sciences and Department of Drugs and Pharmaceuticals School of Pharmaceutical SciencesSa˜o Paulo State UniversityBrazil

Cross-linked pectin/high amylose mixtures were evaluated as a new excipient for matrix tablets formulations,since the mixing of polymers and cross-linking reaction represent rational tools to reach materials with modulated and specific properties that meet specific therapeutic ***:In this work the influence of polymer ratio and cross-linking process on the swelling and the mechanism driving the drug release from swellable matrix tablets prepared with this excipient was ***:Cross-linked samples were characterized by their micromeritic properties(size and shape,density,angle of repose and flow rate)and liquid uptake *** tablets were evaluated according their physical properties and the drug release rates and mechanisms were also ***:Cross-linked samples demonstrated size homogeneity and irregular shape,with liquid uptake ability insensible to ***-linking process of samples allowed the control of drug release rates and the drug release mechanism was influenced by both polymer ratio and cross-linking *** drug release of samples with minor proportion of pectin was driven by an anomalous transport and the increase of the pectin proportion contributed to the erosion of the ***:The cross-linked mixtures of high amylose and pectin showed a suitable excipient for slowing the drug release rates.

关键词： High amylose starch Pectin Cross-linking Swelling Drug delivery mechanism

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In vivo testing of mucus-permeating nanoparticles for oral insulin delivery using Caenorhabditis elegans as a model under hyperglycemic conditions

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Acta Pharmaceutica Sinica B 2021年第4期11卷 989-1002页

作者： ana Lmartínez-López Carlos JGonzález-Navarro Paula Aranaz JoséLVizmanos Juan mIrache NANO-VAC Research Group Department of Chemistry and Pharmaceutical TechnologySchool of Pharmacy and NutritionUniversity of NavarraPamplona 31080Spain Center for Nutrition Research School of Pharmacy and NutritionUniversity of NavarraPamplona 31080Spain Department of Biochemistry&Genetics School of ScienceUniversity of NavarraPamplona 31080Spain Navarra Institute for Health Research(IdiSNA) Pamplona 31080Spain

The aim was to evaluate the potential of mucus-permeating nanoparticles for the oral administration of *** nanocarriers,based on the coating of zein nanoparticles with a polymer conjugate containing PEG,displayed a size of 260 nm with a negative surface charge and an insulin payload of 77 mg/*** intestinal pig mucus,the diffusivity of these nanoparticles(PPA-NPs)was found to be 20-fold higher than bare nanoparticles(NPs).These results were in line with the biodistribution study in rats,in which NPs remained trapped in the mucus,whereas PPA-NPs were able to cross this layer and reach the epithelium *** therapeutic effcacy was evaluated in Caenorhabditis elegans grown under high glucose *** this model,worms treated with insulin-loaded in PPA-NPs displayed a longer lifespan than those treated with insulin free or nanoencapsulated in *** finding was associated with a signifcant reduction in the formation of reactive oxygen species(ROS)as well as an important decrease in the glucose and fat content in *** effects would be related with the mucus-permeating ability of PPA-NPs that would facilitate the passage through the intestinal peritrophic-like dense layer of worms(similar to mucus)and,thus,the absorption of insulin.

关键词： Nanoparticles Oral delivery mucus-permeating Biodistribution Insulin Caenorhabditis elegans ROS

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Oxidative stress modulation in hepatitis C virus infected cells

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World Journal of Hepatology 2015年第29期7卷 2880-2889页

作者： Sonia A Lozano-Sepulveda Owen L Bryan-marrugo Carlos Cordova-Fletes maria C Gutierrez-Ruiz ana m Rivas-Estilla Department of Biochemistry and molecular medicine School of MedicineUniversidad Autonoma de Nuevo LeonMonterreyNuevo Leon 64460Mexico Department of Health Sciences Biological Sciences and Health DivisionSchool of Biological SciencesUniversidad Autonoma Metropolitana

Hepatitis C virus(HCV) replication is associated with the endoplasmic reticulum, where the virus can induce cellular stress. Oxidative cell damage plays an important role in HCV physiopathology. Oxidative stress is triggered when the concentration of oxygen species in the extracellular or intracellular environment exceeds antioxidant defenses. Cells are protected and modulate oxidative stress through the interplay of intracellular antioxidant agents, mainly glutathione system(GSH) and thioredoxin; and antioxidant enzyme systems such as superoxide dismutase, catalase, GSH peroxidase, and heme oxygenase-1. Also, the use of natural and synthetic antioxidants(vitamin C and E, N-acetylcysteine, glycyrrhizin, polyenylphosphatidyl choline, mitoquinone, quercetin, S-adenosylmethionine and silymarin) has already shown promising results as co-adjuvants in HCV therapy. Despite all the available information, it is not known how different agents with antiviral activity can interfere with the modulation of the cell redox state induced by HCV and decrease viral replication. This review describes an evidence-based consensus on molecular mechanisms involved in HCV replication and their relationship with cell damage induced by oxidative stress generated by the virus itself and cell antiviral machinery. It also describes some molecules that modify the levels of oxidative stress in HCV-infected cells.

关键词： Hepatitis C virus Oxidative stress Reactiveoxygen species Vitamin E Antioxidants Glycyrrhizin S-adenosylmethionine N-acetylcysteine Silymarin

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Semantic framework of event detection in emergency situations for smart buildings

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Digital Communications and Networks 2022年第1期8卷 64-79页

作者： Yudith Cardinale Gabriel Freites Edgar Valderrama ana Aguilera Chinnapong Angsuchotmetee Departamento de Computacidn Universidad Simon BolivarCaracasVenezuela Escuela de Ingenieria Informatica Universidad de ValparaisoValparaisoChile Faculty of Science Prince of Songkla University Thailand

multimedia Sensor Networks(mSNs)have enhanced the ability to analyze the environment and provide responses based on its current ***,mSNs are composed of scalar and multimedia sensors that have fixed ***,given the advancement of smart mobile device technologies,it is currently possible to dynamically integrate mobile sensors into *** this paper,we propose a formal platform to manage mSNs and the data gathered from them to detect complex *** main contributions include:m^(2)SSN-Onto,a mobile and multimedia Semantic Sensor Networks Ontology;Py-CEmiD,an engine for detecting complex events and generate reactions to them;a mobile device location engine to locate mobile sensors;and a proof-of-concept in the context of detecting emergency situations in smart *** scenarios are validated for emergency events,combining simulated sensor measurements with real measurements of mobile *** show complex events can be detected in near real time(less than 1 s).

关键词： multimedia sensor network Semantic web Event processing Ontology Geolocalisation

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Evolution of costs of cancer drugs in a Portuguese hospital

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World Journal of Clinical Oncology 2014年第2期5卷 164-169页

作者： Vania Peixoto ana Luísa Faria márcia Gon?alves Joana macedo Sónia Rego Emilio macías Aldiro magano márcia Loureiro António Araújo Department of medical Oncology Centro Hospitalar de Entre Douro e Vouga Pharmacy Department Centro Hospitalar de Entre Douro e Vouga

AIm:To analyze the costs of cancer drugs administered in a Portuguese Hospital compared with the Karolinska Institute ***:To evaluate spending on cancer drugs, we retrospectively analyzed data on the overall costs of cancer drugs, obtained at the Department of medical Oncology of the Centro Hospitalar de Entre Douro e Vouga, between 2004 and 2010. In this comparative study we selected only drugs belonging to the following groups:chemotherapy, targeted therapy, immunotherapy and endocrine therapy. The selected drugs were further grouped according to their market placement year:≤ 1998, 1999 to 2002, 2003 to 2005, and 2006 to 2010. Drugs used as supportive therapy and bisphosphonates were ***:The overall costs of cancer drugs increased gradually between 2004 and 2008(from €1911947 to €3666284), with an increase in the number of patients treated during this period. The expenditure decreased in 2009(€3438155) and increased again in 2010(€3673116), but the costs increment was not the same as in previous years. Chemotherapy and targeted therapy were responsible for most of the expenditure. Drugs placed on the national market before 1999 accounted for more than 50% of the expenditure up to 2007. From 2008, these drugs represented less than 50% of the total expenditure. Cancer drugs placed between 1999 and 2002 accounted for 25%-35% of the costs in all the years studied, while drugs placed between 2003 and 2005 accounted for less than 30%. Drugs placed between 2006 and 2010 were responsible for less than 10% of the ***:In this study, older drugs were responsible for most of the expenditure up to 2007, which is in agreement with the Karolinska study.

关键词： Cancer Costs Drugs Economy Treatment

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Nitrification inhibitor nitrapyrin does not affect yield-scaled nitrous oxide emissions in a tropical grassland

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Pedosphere 2021年第2期31卷 265-278页

作者： ana Gabriela PÉREZ-CASTILLO Cristina CHINCHILLA-SOTO Jorge Alberto ELIZONDO-SALAZAR Ronny BARBOZA Dong-Gill KIm Christoph mÜLLER Alberto SANZ-COBENA Azam BORZOUEI Khadim DAWAR mohammad ZAmAN Environmental Pollution Research Center(CICA) University of Costa RicaMontes de Oca 11501(Costa Rica) Alfredo Volio mata Experimental Station University of Costa RicaOchomogo 30304(Costa Rica) Wondo Genet College of Forestry and Natural Resources Hawassa UniversityP.O.Box 128Shashemene(Ethiopia) Institute of Plant Ecology Justus Liebig University GiessenHeinrich-Buff Ring 26Giessen 35392(Germany) School of Biology and Environmental Science University College DublinBelfieldDublin 4(Ireland) Research Center for the management of Environmental and Agricultural Risks(CEIGRAm) Department of Chemistry and Food Technology(ETSIAAB)Universidad Politécnica de MadridMadrid 28040(Spain) Nuclear Agriculture Research School Nuclear Science and Technology Research Institute(NSTRI)Karaj 31465-1498(Iran) Department of Soil and Environmental Sciences The University of AgriculturePeshawar 25000(Pakistan) Soil and Water management&Crop Nutrition Section Joint Food and Agriculture Organization(FAO)/International Atomic Energy Agency(IAEA)Division of Nuclear Techniques in Food and AgricultureDepartment of Nuclear Sciences and ApplicationsIAEAVienna International CentreP.O.Box 100Vienna 1400(Austria)

Urea is the most common nitrogen(N)fertilizer used in the tropics but it has the risk of high gaseous nitrogen(N)*** of nitrification inhibitor has been suggested as a potential mitigation measure for gaseous N losses in N fertilizer-applied *** a field trial on a tropical Andosol pastureland in Costa Rica,gaseous emissions of ammonia(NH_(3))and nitrous oxide(N_(2)O)and grass yield were quantified from plots treated with urea(U;41.7 kg N ha^(-1)application^(-1))and urea plus the nitrification inhibitor nitrapyrin(U+NI;41.7 kg N ha^(-1)application^(-1)and 350 g of nitrapyrin for each 100 kg of N applied)and control plots(without U and NI)over a six-month period(rainy season).Volatilization of NH_(3)(August to November)in U(7.4%±1.3%of N applied)and U+NI(8.1%±0.9%of N applied)were not significantly different(P>0.05).Emissions of N_(2)O in U and U+NI from June to November were significantly different(Pmission in U+NI was higher than that in *** and crude protein production of grass were significantly higher(Pmission between U(0.31±0.10 g N kg^(-1)dry matter)and U+NI(0.47±0.10 g N kg^(-1)dry matter).The results suggest that nitrapyrin is not a viable mitigation option for gaseous N losses under typical N fertilizer application practices of pasturelands at the study site.

关键词： ammonia volatilization Andosol Costa Rica field trial gaseous N loss greenhouse gas emission urea

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Obesity: Nutrition and Genetics—A Short Narrative Review

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Health 2018年第12期10卷 1779-1788页

作者： José m. Tallon Janine Narciso ana Barros ana Pereira Aldo m. Costa António J. Silva University of Trás-os-montes e Alto Douro Vila Real Portugal University of Beira Interior Covilh&#227 Portugal Polytechnic Institute of Setúbal Superior School of Education Setúbal Portugal Research Centre in Sports Health and Human Development CIDESD Vila Real Portugal Health Science Research Center CICS-UBI Covilh&#227 Portugal

Obesity has become a major global health challenge and it is a risk factor for the development of several comorbid conditions. Additionally, obesity has considerable economic consequences. Obesity is a multifactorial condition that arises from independent influences of genetic and social-environmental factors on food intake and physical activity. It has been difficult to establish clear associations between weight status and the intake of single foods or food groups. In most people, the predisposition to obesity has a polygenic basis, which means that obesity will develop if an individual has several polygenic variants that increase body weight. The FTO gene was the first GWAS-identified obesity-susceptibility gene and since then other polygenic variants that are associated with BmI and dietary intake have also been identified. However, this is still an active area of research as more polygenetic variants await discovery.

关键词： Obesity Nutrition Genetics

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Prenatal and pubertal testosterone exposure imprint permanent modifications in the prostate that predispose to the development of lesions in old mongolian gerbils

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Asian Journal of Andrology 2017年第2期19卷 160-167页

作者： manoel F Biancardi ana PS Perez Cassia RS Caires Luiz R Falleiros Jr Rejane m Goes Patricia SL Vilamaior Diogenes R Freitas Jr Fernanda CA Santos Sebastiao R Taboga Department of Structural and Functional State University of Campinas Av. Bertrand Russel s/n Campinas Sao Paulo 13084864 Brazil 2Department of Histology Embryology and Cell BiologyFederal University of Goias Samambaia II Goiania Goias 74001970 Brazil University Estadual Paulista - UNESP Department of Biology Laboratory of Microscopy and Microanalysis Rua Cristovao Colombo 2265 Sao Jose do Rio Preto Sao Paulo 15054000 Brazil medical School Federal University of Goias Colemar Natal e Silva Goiania Goias 74001970 Brazil

The prostate is an accessory sex gland that develops under precise androgenic control. It is known that hormonal imbalance may disrupt its development predisposing this gland to develop diseases during aging. Although the hypothesis regarding earlier origins of prostate diseases was proposed many years ago, the mechanisms underlying this complex phenomenon are poorly understood. Therefore, the aim of this study was to evaluate the prostates of old male gerbils exposed to testosterone during intrauterine and postnatal life using morphological, biometrical, stereological, Kariometric, immunohistochemical, and immunofluorescence analyses. Our findings demonstrate that prenatal and pubertal exposure to testosterone increases the susceptibility to the development of prostate diseases during aging. The presence of a more proliferative gland associated with foci of adenomatous hyperplasia in animals exposed to testosterone during the prenatal and pubertal phase show that the utero life and the pubertal period are important phases for prostatic morphophysiology establishment, which is a determinant for the health of the gland during aging. Therefore, these findings reinforce the idea that prostate disease may result from hormonal disruptions in early events during prostate development, which imprint permanently on the gland predisposing it to develop lesions in later stages of life.

关键词： adenomatous hyperplasia endocrine-disrupting chemicals gerbil prostate development testosterone

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P2X7 receptor blockade decreases inflammation,apoptosis,and enteric neuron loss during Clostridioides difficile toxin A-induced ileitis in mice

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World Journal of Gastroenterology 2022年第30期28卷 4075-4088页

作者： ana A Q A Santos Deiziane V S Costa Danielle A Foschetti Antoniella S G Duarte Conceicao S martins Pedro m G Soares Patricia Castelucci Gerly A C Brito Department of morphology School of MedicineFederal University of CearaFortaleza 60430-170CearaBrazil Department of Physiology and Pharmacology School of MedicineFederal University of CearáFortaleza 60430-170CearaBrazil Department of Pathology and Legal medicine School of MedicineFederal University of CearaFortaleza 60430-170CearaBrazil Department of morphology(UFC) Federal University of CearaFortaleza 60430-170CearaBrazil Department of anatomy Institute of Biomedical SciencesUniversity of São PauloSao Paulo 05508-270Brazil Department of morphology Federal University of CearaFortaleza 60140-170CearaBrazil

Clostridioides difficile(***)is the most common pathogen causing health care-associated *** TcdA and TcdB have been shown to activate enteric neurons;however,what population of these cells is more profoundly influenced and the mechanism underlying these effects remain *** To characterize a specific population of TcdA-affected myenteric neurons and investigate the role of the P2X7 receptor in TcdA-induced ileal inflammation,cell death,and the changes in the enteric nervous system in *** Swiss mice were used to model TcdA-induced ileitis in ileal loops exposed to TcdA(50μg/Loop)for 4 *** investigate the role of the P2X7 receptor,Brilliant Blue G(50 mg/kg,i.p.),which is a nonspecific P2X7 receptor antagonist,or A438079(0.7μg/mouse,i.p.),which is a competitive P2X7 receptor antagonist,were injected one hour prior to TcdA *** samples were collected to analyze the expression of the P2X7 receptor(by quantitative real-time polymerase chain reaction and immunohistochemistry),the population of myenteric enteric neurons(immunofluorescence),histological damage,intestinal inflammation,cell death(terminal deoxynucleotidyltransferasemediated dUTP-biotin nick end labeling),neuronal loss,and S100B synthesis(immunohistochemistry).RESULTS TcdA upregulated(Pmyenteric neurons compared to that in control *** with the control mice indicated that TcdA promoted(Pmyenteric calretinin+(Calr)and choline acetyltransferase+neurons and increased the number of nitrergic+and Calr+neurons expressing the P2X7 *** of the P2X7 receptor decreased TcdAinduced intestinal damage,cytokine release[interleukin(IL)-1β,IL-6,IL-8,and tumor necrosis factor-α],cell death,enteric neuron loss,and S100B synthesis in the mouse *** Our findings demonstrated that TcdA induced the upregulation of the P

关键词： Clostridioides difficile Clostridioides difficile toxin A P2X7 receptor Enteric nervous system Enteric neuron Enteric glia

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