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Cannabinoid Modulation of Monoamine Levels in Mouse Brain:Unveiling Neurochemical Dynamics through an Innovative High‑performance Liquid Chromatography‑Fluorescence Detection Bioanalysis

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Journal of Analysis and Testing 2024年第3期8卷 300-314页

作者： Fonseca Carla cunha susana Ferreira Ricardo Lapo Pais Mariana Goncalves Joana Camins Antoni Ettcheto Miren Barbosa Rui Fortuna Ana Laboratory of Pharmacology Faculty of PharmacyUniversity of CoimbraPolo das Ciencias da SaudeAzinhaga de Santa CombaCoimbra 3000‑548Portugal CIBIT/ICNAS-Coimbra Institute for Biomedical Imaging and Translational Research University of CoimbraCoimbra 3000‑548Portugal Department of Pharmacology Toxicology and Therapeutic ChemistryFaculty of Pharmacy and Food ScienceUniversitat de BarcelonaBarcelona 08028Spain Institute of Neurosciences Universitat de BarcelonaBarcelona 08035Spain Faculty of Sciences and Technology Doctoral Program in Biomedical EngineeringUniversity of CoimbraCoimbra 3004‑516Portugal Biomedical Research Networking Centre in Neurodegenerative Diseases(CIBERNED) Carlos Ⅲ Health InstituteMadrid 28031Spain Institut d’Investigacio Sanitaria Pere Virgili(IISPV) Reus 43204Spain CNC-Center for Neuroscience and Cell Biology University of CoimbraCoimbra 3004-504Portugal

Homeostasis of monoaminergic pathways is compromised in aging and neurodegenerative/neurological diseases such as Alzheimer’s disease and *** the other hand,their modulation has also been linked to the mechanism of action of several ***,monitoring the levels of noradrenaline(NA),adrenaline(AD),dopamine(DA),and serotonin(5-HT),as well as those of tryptophan(TRYP),the precursor of 5-HT,and DA metabolites,namely 3,4-dihydroxyphenylacetic acid(DOPAC)and homovanillic acid(HVA),is fundamental for assessing disease severity and *** work aimed to develop and validate the first High-Performance Liquid Chromatography(HPLC)coupled with fluorescence detector(FLD)method that simultaneously and accurately quantifies NA,AD,DA,DOPAC,HVA,5-HT and TRYP in mouse brain and prefrontal cortex(PFC)*** sample preparation by protein precipitation was required to extract the *** curves were plotted using the background subtraction approach to reduce the interference of the endogenous *** and inter-day accuracy and precision were within the ranges defined by ICH(The International Council for Harmonisation)guideline for bioanalytical method *** validation,the impact of cannabidiol(CBD),cannabigerol(CBG),and cannabidivarin(CBDV)was explored in mice brains post-administration,revealing significant alterations in specific neurotransmitter levels upon cannabinoid exposure and shedding light on the complex modulation of neurochemical dynamics by *** research highlights the fit-for-purpose of the HPLC-FLD method and provides insights into potential mechanisms underlying phytocannabinoid actions in the central nervous system(CNS).

关键词： Neurotransmitter HPLC Mice Brain Prefrontal cortex Cannabinoid

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Imaging probes for non-invasive tumoral detection and functional monitoring of cancer multidrug resistance

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Cancer Drug Resistance 2020年第2期3卷 209-224页

作者： Filipa Mendes Lurdes Gano Jorge Grilo susana cunha Célia Fernandes António Paulo DECN-Department of Nuclear Engineering and Sciences and C2TN-Center for Nuclear Sciences and Technologies Instituto Superior TécnicoUniversidade de LisboaEstrada Nacional 10Bobadela LRS 2695-066Portugal (Present adress)iMed.Ulisboa-Research Institute for Medicines Faculdade de FarmáciaUniversidade de LisboaAv.Professor Gama PintoLisboa 1649-003Portugal

Aim:Several cationic radiotracers originally developed as myocardial perfusion agents have shown potential for both early detection of cancer and non-invasive monitoring of multiple drug resistance(MDR)by single photon emission computed *** have introduced two cationic complexes,^(99m)Tc-DMEOP[di-methoxy-tris-pyrazolyl-^(99m)Tc-(CO)_(3)]and ^(99m)Tc-TMEOP[tri-methoxy-tris-pyrazolyl-^(99m)Tc-(CO)_(3)],which showed excellent preclinical results as cardiac imaging probes,namely a persistent heart uptake with rapid blood and liver *** study aimed at the evaluation of their usefulness for tumoral detection and functional assessment of ***:The uptake and efflux kinetics of ^(99m)Tc-DMEOP and ^(99m)Tc-TMEOP were evaluated in human prostate,lung,and breast cancer cell lines,including drug-resistant cell lines that are known to overexpress the MDR P-glycoprotein(Pgp).The effects of MDR modulators were also *** vivo studies were performed in xenografted tumor models,and the MDR phenotype of the tumors was confirmed by Western ***:The uptake kinetics of both complexes in human cancer cell lines is comparable with the one found for ^(99m)Tc-Sestamibi,increasing over *** uptake of ^(99m)Tc-TMEOP is greatly reduced in cells overexpressing Pgp and increased in the presence of a Pgp *** nude mice,the tumor uptake of ^(99m)Tc-TMEOP was higher in the MCF-7 xenografts compared with the MCF7 Pgp ***:The uptake kinetics of both complexes in human cancer cell lines is comparable with the one found for ^(99m)Tc-Sestamibi,increasing over *** uptake of ^(99m)Tc-TMEOP is greatly reduced in cells overexpressing Pgp,and increased in the presence of a Pgp *** nude mice,the tumor uptake of ^(99m)Tc-TMEOP was higher in the MCF-7 xenografts compared with the MCF7 Pgp tumors.

关键词： Noninvasive imaging imaging probes tumoral detection multiple drug resistance P-glycoprotein

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Chemical characterisation of particulate matter in urban transport modes

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Journal of Environmental Sciences 2021年第2期33卷 51-61页

作者： Vania Martins Carolina Correia Ines cunha-Lopes Tiago Faria Evangelia Diapouli Manousos Ioannis Manousakas Konstantinos Eleftheriadis susana Marta Almeida Centro de Ciencias e Tecnologias N ucleares Instituto Superior TecnicoLisbonPortugal Institute of Nuclear and Radiological Sciences and Technology Energy and SafetyN.C.S.R.'Demokritos'AthensGreece

Traffic is a main source of air pollutants in urban areas and consequently daily peak exposures tend to occur during *** exposure to particulate matter(PM)was monitored while cycling and travelling by bus,car and metro along an assigned route in Lisbon(Portugal),focusing on PM_(2.5) and PM_(1)0(PM with aerodynamic diameter<2.5 and 10μm,respectively)mass concentrations and their chemical *** vehicles,the indoor-outdoor interplay was also *** PM_(2.5) mean concentrations were 28±5,31±9,34±9 and 38±21μg/m 3 for bus,bicycle,car and metro modes,*** carbon concentrations when travelling by car were 1.4 to 2.0 times higher than in the other transport modes due to the closer proximity to exhaust *** are marked differences in PM chemical composition depending on transport *** particular,Fe was the most abundant component of metro PM,derived from abrasion of rail-wheel-brake *** concentrations of Zn and Cu in cars and buses were related with brake and tyre wear particles,which can penetrate into the *** the motorised transport modes,Fe,Zn,Cu,Ni and K were correlated,evidencing their common traffic-related *** average,the highest inhaled dose of PM_(2.5) was observed while cycling(55μg),and the lowest in car travels(17μg).Cyclists inhaled higher doses of PM_(2.5) due to both higher inhalation rates and longer journey times,with a clear enrichment in mineral *** presented results evidence the importance of considering the transport mode in exposure assessment studies.

关键词： Traffic Commuting Air pollution Particle chemistry Indoor-outdoor interplay Inhaled dose

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Y-chromosome microdeletions in nonobstructive azoospermia and severe oligozoospermia

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Asian Journal of Andrology 2017年第3期19卷 338-345页

作者： Carolina Goncalves Mariana cunha Eduardo Rocha susana Fernandess, Joaquina Silva Luis Ferraz Cristiano Oliveira Alberto Barros Mairio Sousa Department of Biology ClCECO University of Aveiro Campus Universitario de Santiago 3810-193 Aveiro Portugal Department of Microscopy Laboratory of Cell Biology Institute of Biomedical Sciences Abel Salazar University of Porto (ICBAS-UP) Rua Jorge Viterbo Ferreira 228 4050-313 Porto Portugal and Multidisciplinary Unit for Biomedical Research ICBAS-UP Portugal Centre for Reproductive Genetics Prof. Alberto Barros Av. do Bessa 240 1° Dto. Frente 4100-009 Porto Portugal Department of Microscopy Laboratory of Histology and Embryology ICBAS-UP Rua Jorge Viterbo Ferreira 228 4050-313 Porto Portugal Department of Genetics Faculty of Medicine University of Porto Alameda Prof. Hernani Monteiro 4200-319 Porto Portugal and Institute for Innovation and Health Research (13S) University of Porto Portugal Department of Urology Hospital Center of Vila Nova de Gala Rua Conceicao Fernandes 4430-502 Vila Nova de Gala Portugal.

The aim of the present work was to present the outcomes of the patients with Y-chromosome microdeletions treated by intracytoplasmic sperm injection （ICSI）, either using fresh （TESE） or frozen-thawed （TESE-C） testicular sperm and ejaculated sperm （EJAC）. The originality of this work resides in the comparisons between the different types of Y-microdeletions （AZFa, AZFb, and AZFc） and treatments, with detailed demographic, stimulation, embryological, clinical, and newborn （NB） outcomes. Of 125 patients with Y-microdeletions, 33 patients presented severe oligozoospermia （18 performed ICSI with ejaculated sperm） and 92 secretory azoospermia （65 went for TESE with 40 having successful sperm retrieval and performed ICSI）. There were 51 TESE treatment cycles and 43 TESE-C treatment cycles, with a birth of 19 NB （2 in AZFa/TESE-C, 12 in AZFc/TESE, and 5 in AZFc/TESE-C）. Of the 29 EJAC cycles, there was a birth of 8 NB （in AZFc）. In TESE and EJAC cycles, there were no significant differences in embryological and clinical parameters. In TESE-C cycles, there was a significant lower oocyte maturity rate, embryo cleavage rate and mean number of embryos transferred in AZFb, and a higher mean number of oocytes and lower fertilization rate in AZFc. In conclusion, although patients with AZFc microdeletions presented a high testicular sperm recovery rate and acceptable clinical outcomes, cases with AZFa and AZFb microdeletions presented a poor prognosis. Due to the reported heredity of microdeletions, patients should be informed about the infertile consequences on NB and the possibility of using preimplantation genetic diagnosis for female sex selection.

关键词： intracytoplasmic sperm injection newborn outcomes nonobstructive azoospermia severe oligozoospermia testicularsperm extraction Y-chromosome microdeletions

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Modeling of unidirectional blood flow in microvessels with effects of shear-induced dispersion and particle migration

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Applied Mathematics and Mechanics(English Edition) 2022年第10期43卷 1585-1600页

作者： G.ROURE F.R.cunha Laboratory of Microhydrodynamics and Rheology Department of Mechanical EngineeringUniversity of BrasíliaBrasília70910900Brazil Department of Chemical and Biological Engineering University of Colorado BoulderBoulder803090596USA

A cell-free layer,adjacent to microvessel walls,is present in the blood flow in the microcirculation *** layer is of vital importance for the transport of oxygen-saturated red cells to unsaturated *** this work,we first discuss the physics of formation of this cell-free layer in terms of a balance between the shear-induced dispersion and particle *** this end,we use high-viscosity drops as prototypes for cells,and discuss our results in terms of physical parameters such as the viscosity ratio and the capillary *** also provide a short-time analysis of the transient drift-dispersion equation,which helps us better explain the formation process of the cell-free ***,we present models for investigating the blood flow in two different scales of *** investigating the blood flow in venules and arterioles,we consider a continuous core-flow model,where the core-flow solution is considered to be a Casson fluid,surrounded by a small annular gap of Newtonian plasma,corresponding to the cell-free *** also propose a simple model for smaller vessels,such as capillaries,whose diameters are of a few *** this lower-bound limit,we consider a periodic configuration of aligned,rigid,and axi-symmetric cells,moving in a Newtonian *** this regime,we approximate the fluid flow using the lubrication *** intrinsic viscosity of the blood is theoretically predicted,for both the lower and upper-bound regimes,as a function of the non-dimensional vessel diameter,in good agreement with the previous experimental *** compare our theoretical predictions with the experimental data,and obtain qualitatively good agreement with the well-known Fåhræus-Lindqvist effect.A possible application of this work could be in illness diagnosis by evaluating changes in the intrinsic viscosity due to blood abnormalities.

关键词： theory flow dispersion

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Comparison of Classical Models for Evaluating the Heat Requirements of Olive(Olea europeae L.) in Portugal

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Journal of Integrative Plant Biology 2006年第6期48卷 664-671页

作者： Helena Ribeiro Mário cunha Ilda Abreu Autonomous Section of Agricultural Sciences Faculty of Sciences University of Porto4485-661 VairaoPortugal Department of Botany Faculty of SciencesUniversity of Porto1191-4150 PortoPortugal Institute of Agricultural Sciences and Technology 4485-661 VairaoPortugal Department of Botany Faculty of Sciences University of Porto1191-4150 PortoPortugal Institute for Molecular and Cell Biology 823-4150 PortoPortugal

The aim of the present study was to compare the accuracy and reproducibility of six statistical models for the calculation of olive （Olea europeae L.） heat requirements to trigger the onset of flowering in three Portuguese regions： Reguengos de Monsaraz, Valenga do Douro, and Braga. Other alms were to ascertain the date on which the heat-accumulation period started and the threshold temperatures above which the development of reproductive structures starts in olives. The starting and peak dates for the regional O. europeae flowering season were estimated by monitoring airborne pollen from 1998 to 2004 using ＂Cour＂- type samplers. The threshold temperature values calculated for the three regions were very similar （9.0 ℃ for Valenca do Douro, 9.2 ℃ for Reguengos de Monsaraz, and 9.7 ℃ for Braga）. The accumulated daily mean temperature model had less interannual and inter-regional variation, showing best predictive results for 2004, with absolute differences between the observed and predicted dates of 4 d in Reguengos de Monsaraz and 2 d In Valenca do Douro and Braga for the onset of flowering date and of 2 d In Reguengos de Monsaraz, 7 d in Valenca do Douro, and 4 d in Braga for peak flowering dates. This model was the most accurate, reproducible, and operational to calculate heat requirements for olives to flower, with an average mean temperature accumulation of 1 446 ℃ In Reguengos, 1 642 ℃ in Valenga do Douro, and 1 703℃ In Braga to reach the onset of flowering. The best initial date for this accumulation was 1 January.

关键词： flowering season heat requirements olives pollen Portugal

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Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

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Neural Regeneration Research 2024年第11期19卷 2365-2376页

作者： Victoria cunha Alves Eva Carro Joana Figueiro-Silva Neurodegenerative Diseases Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Network Center for Biomedical Research Neurodegenerative Diseases(CIBERNED)MadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurotraumatology and Subarachnoid Hemorrhage Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research Into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpain Institute of Medical Genetics University of ZurichZurichSwitzerland Department of Molecular Life Science University of ZurichZurichSwitzerland

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA *** review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease *** examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease *** entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the ***,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal ***,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory *** complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation *** the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease *** research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

关键词： Alzheimer’s disease ANK1 BIN1 DNA methylation epigenome-wide association studies HOXA3 MCF2L RHBDF2

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Evaluation of ancestry from human skeletal remains: a concise review

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Forensic Sciences Research 2020年第2期5卷 89-97页

作者： Eugenia cunha Douglas HUbelaker National Institute of Legal Medicine and Forensic Sciences LisbonPortugal Laboratory of Forensic Anthropology Centre for Functional EcologyDepartment of Life SciencesUniversity of CoimbraCoimbraPortugal Department of Anthropology National Museum of Natural HistorySmithsonian InstitutionWashingtonDCUSA

Ancestry assessment represents a major component of forensic anthropological analysis of recovered human *** of ancestry,together with other aspects of the biological profile,can help narrow the search of missing persons and contribute to eventual positive *** information can prove useful to authorities involved in the identification and investigative process since many lists of missing persons have a reference to this *** research has strengthened available methodologies involving metric,non-metric morphological as well as chemical and genetic *** review addresses the new anthropological techniques that are now available,as well as the complex historical context related to ancestry evaluation.

关键词： Forensic sciences forensic anthropology ancestry estimation skeletal remains

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G protein-coupled receptor 37(GPR37) emerges as an important modulator of adenosinergic transmission in the striatum

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Neural Regeneration Research 2019年第11期14卷 1912-1914页

作者： Xavier Morato Rodrigo A. cunha Francisco Ciruela Unitat de Farmacologia Departament Patologia i Terapeutica ExperimentalFacultat de MedicinaInstituto de Investigacion Biomedica de Bellvitge (IDIBELL)Universitat de BarcelonaL’Hospitalet de LlobregatBarcelonaSpainInstitut de NeurocienciesUniversitat de BarcelonaBarcelonaSpain (Morato X Ciruela F) Center for Neuroscience and Cell Biology (CNC)-Center for Neurosciences and Cell BiologyUniversity of CoimbraCoimbraPortugalFaculty of MedicineUniversity of CoimbraCoimbraPortugal

G protein-coupled receptor 37 (GPR37), also known as parkin associated endothelin-like (Pael) receptor, is an orphan G protein- coupled receptor, which suffers a defective parking ubiquitination in autosomal recessive Parkinson’s disease promoting its endoplasmic reticulum aggregation and stress, neurotoxicity and neuronal death (Takahashi and Imai, 2003). Interestingly, we have demonstrated previously that GPR37 heteromerizes with adenosine A2A receptor (A2AR) in the striatum (Morato et al., 2017;Sokolina et al., 2017).

关键词： G protein-coupled receptor 37(GPR37) important modulator adenosinergic transmission

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Siderophore-Producing Rhizobacteria as a Promising Tool for Empowering Plants to Cope with Iron Limitation in Saline Soils:A Review

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Pedosphere 2019年第4期29卷 409-420页

作者： Maria J.FERREIRA Helena SILVA Angela cunha Biology Department and Centre for Environmental and Marine Studies(CESAM) University of Aveiro Campus de Santigo

Iron(Fe) bioavailability to plants is reduced in saline soils;however, the exact mechanisms underlying this effect are not yet completely understood. Siderophore-expressing rhizobacteria may represent a promising alternative to chemical fertilizers by simultaneously tackling salt-stress effects and Fe limitation in saline soils. In addition to draught, plants growing in arid soils face two other major challenges: high salinity and Fe deficiency. Salinity attenuates growth, affects plant physiology, and causes nutrient imbalance,which is, in fact, one of the major consequences of saline stress. Iron is a micronutrient essential for plant development, and it is required by several metalloenzymes involved in photosynthesis and respiration. Iron deficiency is associated with chlorosis and low crop productivity. The role of microbial siderophores in Fe supply to plants and the effect of plant growth-promoting rhizobacteria(PGPR) on the mitigation of saline stress in crop culture are well documented. However, the dual effect of siderophore-producing PGPR, both on salt stress and Fe limitation, is still poorly explored. This review provides a critical overview of the combined effects of Fe limitation and soil salinization as challenges to modern agriculture and intends to summarize some indirect evidence that argues in favour of siderophore-producing PGPR as biofertilization agents in salinized soils. Recent developments and future perspectives on the use of PGPR are discussed as clues to sustainable agricultural practices in the context of present and future climate change scenarios.

关键词： aridity bioavailability biofertilizer Fe deficiency high salinity plant growth-promoting rhizobacteria(PGPR) saline stress soil salinization

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