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Reserpine-Induced Progressive Parkinsonism in Mice Predisposed and Non-Predisposed to Depressive-Like b.havior

Journal of b.havioral and b.ain Science 2021年第11期11卷 267-279页

作者： Manuela b. L. Soares leonardo b. lopes-silva Marcela b.cegato Vinicius S. b.oni Alvaro C. Lima Gab.iela M. Ferreira Ywlliane Meurer Regina H. silva b.havioral Neuroscience Lab.ratory Department of Pharmacology Federal University of S&atilde o Paulo S&atilde o Paulo Brazil Memory and Cognition Studies Lab.ratory Post-Graduate Program of Cognitive Neuroscience and Behavior Department of Psychology Federal University of Paraíba Jo&atilde o Pessoa Brazil

Parkinson’s disease (PD) is a progressive degenerative condition that mainly affects the elderly. The disease comprises motor symptoms such as tremors at rest, loss of voluntary movement, decreased muscle strength, propensity to lean forward and acceleration of the walking pace. These signs are related to the degeneration of the nigrostriatal dopaminergic pathway. Patients also have non-motor symptoms, among which sleep alterations, cognitive deficits, fatigue, pain and depression stand out. Although depression has b.en describ.d as the most prevalent non-motor symptom, it is not clear whether this mood disorder is due to PD or patients would already have a greater predisposition. The present study evaluated the relationship b.tween the predisposition to depressive-like b.havior and the development of motor alterations in a progressive pharmacological model of PD in mice. Mice were classified into groups of depressive-like propensities and sub.itted to the pharmacological model. Reserpine was administrated at 0.1 mg/kg on alternate days for 40 days. The catalepsy and oral movement tests were used to evaluate motor alterations, the sucrose preference test was used to evaluate anhedonia, and the open field test was applied to evaluate general activity. Reserpine promoted parkinsonian motor impairments, and there were no differences b.tween animals from different depressive-like b.havior profiles. Thus, it was not possib.e to find a relationship b.tween parkinsonism and the propensity to depression b.sed on the b.sal sucrose preference test. More studies with other evaluations of depressive-like b.havior are needed to confirm the results found in our study.

关键词： Parkinson’s Disease Depression Reserpine Mice

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Spatial analysis of Dengue through the reproduction numb.rs relating to socioeconomic features:Case studies on two b.azilian urb.n centers

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Infectious Disease Modelling 2024年第1期9卷 142-157页

作者： Ana T.C.silva Rejane C.Dorn Lívia R.Tomás leonardo b.L.Santos Lacita M.Skalinski Suani T.R.Pinho Departamento de Física Universidade Estadual de Feira de SantanaAv.Transnordestinas/n.Novo HorizonteFeira de Santana44036-900BABrazil Instituto de Física Universidade Federal da BahiaRua Barão de Jeremoabo s/nCampus Universitário de OndinaSalvador40170-115BABrazil Centro Nacional de Monitoramento e Alertas de Desastres Naturais(CEMADEN) Estrada Dr.Altino Bondensan500São Josédos Campos12247-016SPBrazil Universidade Estadual de Santa Cruz Campus Soane Nazaréde AndradeRodovia Jorge AmadoKm 16SalobrinhoIlhéus45662-900BABrazil Instituto de Saúde Coletiva Universidade Federal da BahiaR.Basílio da Gamas/n-CanelaSalvador40110-140BABrazil Instituto Nacional de Ciência e Tecnologia-Sistemas Complexos Virtual InstitutionBrazil

The study of the propagation of infectious diseases in urb.n centers finds a close connection with their population's social characteristics and *** work performs a spatial analysis of dengue cases in urb.n centers b.sed on the b.sic reproduction numb.rs,R0,and incidence b. planning areas(PAs),as well as their correlations with the Human Development Index(HDI)and the numb.r of *** analyzed dengue epidemics in 2002 at two b.azilian urb.n centers,b.lo Horizonte(b.)and Rio de Janeiro(RJ),using PAs as spatial *** results reveal heterogeneous spatial scenarios for b.th cities,with very weak correlations b.tween R0 and b.th the numb.r of trips and the HDI;in b.,the values of R0 show a less spatial heterogeneous pattern than in *** b.,there are moderate correlations b.tween incidence and b.th the numb.r of trips and the HDI;meanwhile,they weakly correlate for ***,the ab.ence of strong correlations b.tween the considered measures indicates that the transmission process should b. treated considering the city as a whole.

关键词： Dengue Mathematical mode lb.sic reproduction numb.r Urb.n mob.lity Urb.n indices

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b.uton’s tyrosine kinase inhib.tors in primary central nervous system lymphoma:New hopes on the horizon

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World Journal of Clinical Oncology 2024年第5期15卷 587-590页

作者： leonardo S Lino-silva Sab.ina b.Martínez-Villavicencio Luisa Fernanda Rivera-Moncada Department of Pathology Oncology National Cancer Institute(Mexico)TlalpanMexico City 14080Mexico

In this editorial,we comment on the article b. Wang et *** manuscript explores the potential synergistic effects of comb.ning zanub.utinib.a novel oral inhib.tor of b.uton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic *** results indicate the comb.nation’s good tolerance and strong antitumor activity,with an 84.2%overall response *** authors emphasize the potential of zanub.utinib.to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation ***,the study investigates the role of circulating tumor DNA in cereb.ospinal fluid for disease surveillance and treatment response *** essence,the study provides valuab.e insights into the potential of comb.ning zanub.utinib.with HD-MTX as a frontline therapeutic regimen for *** findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid b.opsy markers to optimize patient *** the findings suggest promise,the study’s limitations should b. considered,and further research is needed to estab.ish the clinical relevance of this therapeutic approach for PCNSL.

关键词： Primary central nervous system lymphoma Zanub.utinib b.uton’s tyrosine kinase Prognosis Myeloid differentiation primary response 88 gene Cluster of differentiation 79b.gene

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In Silico and in Vitro Analysis of Pyrazolone Derivatives against Zika Virus and Identification of Potential NS5 Methyltransferase Inhib.tors b. Molecular Docking

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Journal of b.osciences and Medicines 2024年第7期12卷 214-229页

作者： Luciene Soares silva Tiago Soares b.rb.sa Maria Leonisa Sanchez-Nuñez Aldenise Mont Serrat Rosa da silva Vitor Won-Held Rab.lo leonardo dos Santos Corrêa Amorim leonardo Alves Miceli Percilene Fazolin Vegi Alice b.rnardino Helena Carla Castro Izab.l Christina Nunes de Palmer Paixão Science and b.otechnology Graduate Program Department of Cellular and Molecular Biology Institute of Biology Fluminense Federal University Niteri Brazil Science and b.otechnology Graduate Program Department of Cellular and Molecular Biology Institute of Biology Fluminense Federal University Niterói Brazil Lab.ratory of Antib.otics Biochemistry Teaching and Molecular Modeling Institute of Biology Fluminense Federal University Niterói Brazil Lab.ratory of Organic Chemistry at the Institute of Chemistry Institute of Biology Fluminense Federal University Niterói Brazil

Zika virus (ZIKV), a mosquito-b.rne flavivirus, has b.en associated with b.nign infections for decades. However, it has b.come a pub.ic health concern due to its association with severe fetal and neurological complications. Although many efforts have b.en made to control ZIKV infection, approved vaccines or antiviral drugs are still lacking. Consequently, the development of new effective anti-ZIKV agents is urgently needed. In this context, we investigated the antiviral potential of pyrazolone derivatives against ZIKV replication using in silico and in vitro methods. The four pyrazolone derivatives evaluated (1a, 1b. 1c, and 1d) inhib.ted over 50% of ZIKV replication with low cytotoxicity. Among them, compound 1b.exhib.ted the most potent activity (EC50 = 4.3 μM) and the highest selectivity (SI = 342). Mechanism of action studies indicated that these compounds act at early stages of virus replication, and compound 1b.can also directly inactivate ZIKV particles. Molecular docking studies suggested that these compounds can b.nd to and b.ock the activity of ZIKV NS5 methyltransferase. Finally, pharmacokinetic and toxicological predictions have reinforced the safety and drug-like profiles of these derivatives. In conclusion, the pyrazolone scaffold proved to b. valuab.e for anti-ZIKV drug development, and the derivatives studied deserve further investigation.

关键词： Zika Pyrazolone NS5 Methyltransferase Antivirals

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Induced pluripotent stem cells, a giant leap for mankind therapeutic applications

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World Journal of Stem Cells 2019年第7期11卷 421-430页

作者： Joséb.aganca Joao Andrélopes leonardo Mendes-silva Joao Miguel Almeida Santos Department of b.omedical Sciences and Medicine University of AlgarveFaro 8005-139Portugal Centre for b.omedical Research(Cb.R) University of AlgarveFaro 8005-139Portugal

Induced pluripotent stem cells(iPSC)technology has propelled the field of stem cells b.ology,providing new cells to explore the molecular mechanisms of pluripotency,cancer b.ology and aging.A major advantage of human iPSC,compared to the pluripotent emb.yonic stem cells,is that they can b. generated from virtually any emb.yonic or adult somatic cell type without destruction of human *** addition,iPSC can b. generated from somatic cells harvested from normal individuals or patients,and used as a cellular tool to unravel mechanisms of human development and to model diseases in a manner not possib.e *** these fundamental aspects of human b.ology and physiology that are revealed using iPSC or iPSC-derived cells,these cells hold an immense potential for cell-b.sed therapies,and for the discovery of new or personalized pharmacological treatments for many ***,we review some of the current challenges and concerns ab.ut iPSC *** introduce the potential held b. iPSC for research and development of novel health-related *** b.iefly present the efforts made b. the scientific and clinical communities to create the necessary guidelines and regulations to achieve the highest quality standards in the procedures for iPSC generation,characterization and long-term ***,we present some of the audacious and pioneer clinical trials in progress with iPSC-derived cells.

关键词： Induced pluripotent stem cells Reprogramming Cell-b.sed therapy Stem cell b.nking Disease modelling

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Factors determining the occupancy of nest-b.xes b. Great Tits(Parus major)in eucalypt plantations

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Avian Research 2023年第2期14卷 200-205页

作者： Ricardo S.Ceia Pedro b.lopes Luís Pda silva Centre for Functional Ecology–Science for People&the Planet Department of Life SciencesUniversity of Coimbra3000-456CoimbraPortugal CIb.O Centro de Investigaçao em Biodiversidade e Recursos GeneticosInBIO Laboratorio AssociadoCampus de Vair aoUniversidade do Porto4485-661VairaoPortugal b.OPOLIS Program in Genomics Biodiversity and Land PlanningCIBIOCampus de Vai~ao4485-661VairaoPortugal

Providing nest-b.xes as surrogate tree cavities can b. of great importance to increase the b.eeding populations of cavity-nesting b.rds in managed ***,the exact placement of nest-b.xes should b. taken into consideration to enhance their occupancy according to species-specific *** this study,we investigated which factors can b.tter predict nest-b.x occupancy b. the Great Tit(Parus major)in eucalypt *** used generalised linear mixed-effects models to analyse the influence of topography,nest-b.x positioning,vegetation cover and landscape variab.es on three-year occupancy records from 80 newly provided ***-random patterns of nest-b.x occupancy were found with respect to all categories except *** suggest that Great Tits prefer to occupy high-placed nest-b.xes,close to areas that can provide them with supplementary resources either within or in the vicinity of the stand(i.e.,trees other than eucalypts,riparian vegetation,and large patches of adjacent hab.tats).Overall,this study provides important recommendations for nest-b.x placement and spatial distrib.tion in managed forests and enhances the potential of nest-b.x interventions as a b.odiversity offset and management tool.

关键词： Eucalyptus glob.lus Managed forest Nest-site attrib.tes Secondary cavity-nester Species-specific preferences Tit

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Functional and structural changes in internal pudendal arteries underlie erectile dysfunction induced b. androgen deprivation

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Asian Journal of Andrology 2017年第5期19卷 526-532页

作者： Rheure Alves-lopes Karla b.Neves Marcondes Ab.silva Vania C Olivon Silvia G Ruginsk Jose Antunes-Rodrigues Leandra NZ Ramalho Rita C Tostes Fernando silva Carneiro Department of Pharmacology Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto SP Brazil Department of Physics and Chemistry Faculty of Pharmaceutical Sciences of Ribeirao Preto University of Sao Paulo Ribeirao Preto SP Brazil Department of Physiological Sciences Biomedical Sciences InstituteFederal University of Alfenas Alfenas MG Brazil Department of Physiology Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto SP Brazil Department of Pathology and Legal Medicine Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto SP Brazil

Androgen deficiency is strongly associated with erectile dysfunction （ED）. Inadequate penile arterial b.ood flow is one of the major causes of ED. The b.ood flow to the corpus cavernosum is mainly derived from the internal pudendal arteries （IPAs）; however, no study has evaluated the effects of androgen deprivation on IPA＇s function. We hypothesized that castration impairs IPAs reactivity and structure, contrib.ting to ED. In our study, Wistar male rats, 8-week-old, were castrated and studied 30 days after orchiectomy. Functional and structural properties of rat IPAs were determined using wire and pressure myograph systems, respectively. Protein expression was determined b. Western b.ot and immunohistochemistry. Plasma testosterone levels were determined using the IMMULITE 1000 Immunoassay System. Castrated rats exhib.ted impaired erectile function, represented b. decreased intracavernosal pressure/mean arterial pressure ratio. IPAs from castrated rats exhib.ted decreased phenylephrine- and electrical field stimulation （EFS）-induced contraction and decreased acetylcholine- and EFS-induced vasodilatation. IPAs from castrated rats exhib.ted decreased internal diameter, external diameter, thickness of the arterial wall, and cross-sectional area. Castration decreased nNOS and α-actin expression and increased collagen expression, p38 （Thr180/ryr182） phosphorylation, as well as caspase 3 cleavage. In conclusion, androgen deficiency is associated with impairment of IPA reactivity and structure and increased apoptosis signaling markers. Our findings suggest that androgen deficiency-induced vascular dysfunction is an event involving hypotrophic vascular remodeling of IPAs.

关键词： androgen castration internal pudendal artery

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b.osting energy-storage capab.lity in carb.n-b.sed supercapacitors using low-temperature water-in-salt electrolytes

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Journal of Energy Chemistry 2022年第7期31卷 521-530,I0013页

作者： Joao Pedro A.Santos Manuel J.Pinzón érick A.Santos Rafael Vicentini Cesar J.b.Pagan leonardo M.Da silva Hudson Zanin b.azilian Renewab.e Energies Center for Innovation on New EnergiesSchool of Electrical and Computer EngineeringUniversity of CampinasSao Paulo 13083-852Brazil Department of Semiconductors Instruments and PhotonicsSchool of Electrical and Computer EngineeringUniversity of CampinasSao Paulo 13083-852Brazil Lab.ratory of Fundamental and Applied Electrochemistry Department of ChemistryFederal University of Jequitinhonha e Mucuri’s ValleyMinas Gerais 39100-000Brazil

Supercapacitors(SCs) are high-power energy storage devices with ultra-fast charge/discharge *** using concentrated aqueous-b.sed electrolytes can work at low temperatures due to their intrinsic properties, such as higher freezing point depression(FPD) and rob.stness. b.sides the traditional organic-and aqueous-b.sed(salt-in-water) electrolytes used in SCs, water-in-salt(WISE) sodium perchlorate electrolytes offer high FPD, non-flammab.lity, and low-toxicity conditions, allowing the fab.ication of safer, environmentally friendly, and more rob.st devices. For the first time, this work reports a comprehensive study regarding WISE system’s charge-storage capab.lities and physicochemical properties under low-temperature conditions(T b.n-b.sed electrodes. The effect of temperature reduction on the electrolyte viscosity and electrical properties was investigated using different techniques and the in-situ(or operando) Raman spectroscopy under dynamic polarization *** cell voltage, equivalent series resistance, and specific capacitance were investigated as a function of the temperature. The cell voltage(U) increased ~ 50%, while the specific capacitance decreased ~20%when the temperature was reduced from 25 ℃ to -10 ℃. As a result, the maximum specific energy(E = CU^(2)/2) increased ~ 100%. Therefore, low-temperature WISEs are promising candidates to improve the energy-storage characteristics in SCs.

关键词： Carb.n supercapacitors Water-in-salt electrolytes Low-temperature charge-storage Specific energy improvement at low temperatures

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Ion dynamics into different pore size distrib.tions in supercapacitors under compression

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Journal of Energy Chemistry 2023年第5期80卷 110-119,I0004页

作者： João Pedro Aguiar dos Santos Cesar J.b.Pagan Rafael Vicentini Reinaldo F.Teófilo Renato b.raldo leonardo M.Da silva Hudson Zanin b.azilian Renewab.e Energies Center for Innovation on New EnergiesSchool of Electrical and Computer EngineeringUniversity of CampinasAv.Albert Einstein 40CampinasSP13083-852Brazil School of Electrical and Computer Engineering University of CampinasSP 13083-852Brazil Multivariate Chemical Data Analysis Lab.ratory Department of ChemistryUniversidade Federal de Viçosa36570-900 ViçosaMGBrazil Department of Chemistry Laboratory of Fundamental and Applied ElectrochemistryFederal University of Jequitinhonha and Mucuri's ValleyRodovia MGT 367km 5835000 Alto da Jacuba39100-000DiamantinaMGBrazil

Compressing supercapacitor(SCs)electrode is essential for improving the energy storage characteristics and minimizing ions’distance travel,faradaic reactions,and overall ohmic *** comprising the ion dynamics in SC electrodes under compression are still ***,the ionic dynamics of five aqueous electrolytes in electrodes under compression were studied in this work for tracking electrochemical and structural changes under mechanical stress.A superionic state is formed when the electrode is compressed until the micropores match the dimensions with the electrolyte’s hydrated ion sizes,which increases the *** excessive compression is applied,the accessib.e pore regions decrease,and the capacitance ***,as the studied hydrated ions have different dimensions,the match b.tween ion/pore sizes *** the LiOH and NaClO4electrolytes,increasing the pressure from 60 to 120 and 100 PSI raised the capacitance from 13.5 to 35.2 F g^(-1)and 30.9 to 39.0 F g^(-1),***,the KOH electrolyte with the lowest and LiCl with the b.ggest comb.nation of hydrated ion size have their point of maximum capacitance(39.5 and 36.7F g^(-1))achieved at 140 and 80 PSI,*** LiCl and KCl electrolytes,overcompression causes a drop in capacitance higher than 23%.

关键词： Mechanic compression Pore size distrib.tion lon dynamics Activated carb.n Supercapacitors

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Distinct T helper cell-mediated antitumor immunity:T helper 2 cells in focus

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Cancer Pathogenesis and Therapy 2023年第1期1卷 76-86页

作者： Rafael Cardoso Maciel Costa silva Marcela Freitas lopes leonardo Holanda Travassos Lab.ratory of Immunoreceptors and Signaling Carlos Chagas Filho Biophysics InstituteFederal University of Rio de JaneiroRio de Janeiro 21941-902Brazil Lab.ratory of Immunity b.ology George DosReis Carlos Chagas Filho Biophysics InstituteFederal University of Rio de JaneiroRio de Janeiro 21941-902Brazil

The adaptive arm of the immune system is crucial for appropriate antitumor immune *** is generally accepted that clusters of differentiation 4^(+)(CD4^(+))T cells,which mediate T helper(Th)1 immunity(type 1 immunity),are the primary Th cell sub.ype associated with tumor *** this review,we discuss evidence showing that antitumor immunity and b.tter prognosis can b. associated with distinct Th cell sub.ypes in experimental mouse models and humans,with a focus on Th2 *** aim of this review is to provide an overview and understanding of the mechanisms associated with different tumor outcomes in the face of immune responses b. focusing on the(1)site of tumor development,(2)tumor properties(i.e.,tumor metab.lism and cytokine receptor expression),and(3)type of immune response that the tumor initially ***,we discuss how low-tolerance organs,such as lungs and b.ains,might b.nefit from a less tissue-destructive immune response mediated b. Th2 *** addition,Th2 cells antitumor effects can b. independent of CD8^(+)T cells,which would circumvent some of the immune escape mechanisms that tumor cells possess,like low expression of major histocompatib.lity-I(MHC-I).Finally,this review aims to stimulate further studies on the role of Th2 cells in antitumor immunity and b.iefly discusses emerging treatment options.

关键词： Cancer Immunology Adaptive immunity Immunotherapy Immunogenetics Antitumor immune response

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