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NT157 has antineoplastic effects and inhibits IRS1/2 and STAT3/5 in JAK2^(V617F)-positive myeloproliferative neoplasm cells

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2440-2449页

作者： bruna alves fenerich Jaqueline Cristina Fernandes Ana Paula Nunes Rodrigues alves Juan Luiz Coelho-Silva Renata Scopim-Ribeiro Priscila Santos Scheucher Christopher A.Eide Cristina E.Tognon Brian J.Druker Eduardo Magalhães Rego João Agostinho Machado-Neto Fabiola Traina Department of Medical Images Hematologyand Clinical OncologyUniversity of Sao Paulo at Ribeirao Preto Medical SchoolRibeirao PretoSao PauloBrazil Center for Cell-Based Therapy Sao Paulo Research FoundationRibeirao PretoSao PauloBrazil Knight Cancer Institute Oregon Health&Science UniversityPortlandORUSA Howard Hughes Medical Institute PortlandORUSA Department of Internal Medicine University of Sao Paulo Medical SchoolSao PauloBrazil Department of Pharmacology Institute of Biomedical Sciences of the University of Sao PauloSao PauloBrazil

Recent data indicate that IGF1R/IRS signaling is a potential therapeutic target in BCR-ABL1-negative myeloproliferative neoplasms(MPN);in this pathway,IRS2 is involved in the malignant transformation induced by JAK2^(V617F),and upregulation of IGF1R signaling induces the MPN ***157,a synthetic compound designed as an IGF1R-IRS1/2 inhibitor,has been shown to induce antineoplastic effects in solid ***,we aimed to characterize the molecular and cellular effects of NT157 in JAK2^(V617F)positive MPN cell lines(HEL and SET2)and primary patient hematopoietic *** JAK2^(V617F)cell lines,NT157 decreased cell viability,clonogenicity,and cell proliferation,resulting in increases in apoptosis and cell cycle arrest in the G2/M phase(p<0.05).NT157 treatment inhibited IRS1/2,JAK2/STAT,and NFκB signaling,and it activated the AP-1 complex,downregulated four oncogenes(CCND1,MYB,WT1,and NFKB1),and upregulated three apoptotic-related genes(CDKN1A,FOS,and JUN)(p<0.05).NT157 induced genotoxic stress in a JAK2/STAT-independent ***157 inhibited erythropoietin-independent colony formation in cells from polycythemia vera patients(p<0.05).These findings further elucidate the mechanism of NT157 action in a MPN context and suggest that targeting IRS1/2 proteins may represent a promising therapeutic strategy for MPN.

关键词： JAK2 IGF1R neoplasms STAT3

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Physiology and health assessment,risk balance,and model for endstage liver disease scores:Postoperative outcome of liver transplantation

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World Journal of Transplantation 2025年第1期15卷 86-94页

作者： Raquel Hohenreuther Andresa ThoméSilveira Edison Moraes Rodrigues Filho Anderson Garcez bruna Goularth Lacerda Sabrina alves Fernandes Claudio Augusto Marroni Postgraduate Program in Hepatology Universidade Federal de Ciências da Saúde de Porto AlegrePorto Alegre 90050-170Brazil Department of Intensive Medicine Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Brazil Department of Public Health University of Vale do Rio dos SinosSao Leopoldo 93022-750Brazil

BACKGROUND Liver transplantation aims to increase the survival of patients with end-stage liver diseases and improve their quality of *** number of organs available for transplantation is lower than the *** provide fair organ distribution,predictive mortality scores have been *** To compare the Acute Physiology and Chronic Health Evaluation IV(APACHE IV),balance of risk(BAR),and model for end-stage liver disease(MELD)scores as predictors of *** Retrospective cohort study,which included 283 adult patients in the postoperative period of deceased donor liver transplantation from 2014 to *** The transplant recipients were mainly male,with a mean age of 58.1 *** were mostly male,with a mean age of 41.6 *** median cold ischemia time was 3.1 hours,and the median intensive care unit stay was 5 *** APACHE IV,a mean of 59.6 was found,BAR 10.7,and MELD *** 28-day mortality rate was 9.5%,and at 90 days,it was 3.5%.The 28-day mortality prediction for APACHE IV was very good[area under the curve(AUC):0.85,P<0.001,95%CI:0.76-0.94],P<0.001,BAR(AUC:0.70,P<0.001,95%CI:0.58–0.81),and MELD(AUC:0.66,P<0.006,95%CI:0.55-0.78),P<*** 90 days,the data for APACHE IV were very good(AUC:0.80,P<0.001,95%CI:0.71–0.90)and moderate for BAR and MELD,respectively,(AUC:0.66,P<0.004,95%CI:0.55–0.77),(AUC:0.62,P<0.026,95%CI:0.51–0.72).All showed good discrimination between deaths and *** for the best value for liver transplantation,it was significant only for APACHE IV(P<0.001).CONCLUSION The APACHE IV assessment score was more accurate than BAR and MELD in predicting mortality in deceased donor liver transplant recipients.

关键词： Liver transplantation Acute physiology and chronic health evaluation IV Balance of risk Model for end-stage liver disease Mortality Intensive care unit

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Biochar influences the cane fields’microbiota and the development of pre-sprouted sugarcane seedlings

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Waste Disposal and Sustainable Energy 2023年第1期5卷 75-88页

作者： bruna Cristina Pinto Adriana Barboza alves Osania Emerenciano Ferreira Gustavo Henrique Gravatim Costa Magno Andréde Oliveira Augusto Cesar da Silva Bezerra Alan Rodrigues Teixeira Machado Postgraduate Program in Environmental Sciences State University of Minas GeraisFrutal UnityFrutalMinas Gerais38202-436Brazil Department of Agricultural and Biological Sciences State University of Minas GeraisFrutal UnityFrutalMinas Gerais38208-436Brazil Postgraduate Program in Geotechnical Engineering Federal University of Ouro PretoOuro PretoMinas Gerais35400-000Brazil Department of Transport Engineering Federal Center for Technological Education of Minas GeraisBelo HorizonteMinas Gerais30421-169Brazil Department of Exact Sciences State University of Minas GeraisJoão Monlevade UnityJoão MonlevadeMinas Gerais35930-314Brazil

This research investigates the soil conditioning effect of sugar cane fields with biochar produced from sugarcane *** influence on the physicochemical and microbiological conditions of the soil and the agronomic performance of sugarcane seedlings was *** this end,the biochar from sugarcane bagasse was produced by pyrolysis in a double drum oven and mixed with soil at rates of 0,1%,3%,and 5%(in weight).The experiment was installed in a greenhouse with two evaluation periods(30 days and 60 days)and five *** pot received a pre-sprouted cane seedling,and the analysis of colony-forming units(bacteria and fungi),physicochemical characteristics of the soil,and growth and development of sugarcane were performed per *** biochar showed a high fixed carbon content(72%)and a specific surface area estimated by the adsorption of methylene blue of 50 m2 g−***,its structure is porous and contains important nutrients(e.g.,CaO,K2O,and P2O5).In the periods evaluated,the applications of the 3%and 5%(in weight)rates of biochar reduced most of the soil fertility ***,the chemical analyses indicated that the sugarcane field soil collected already possessed high *** microbiota was influenced,but only the application of the 3%(in weight)rate at 60 days after planting showed a significant positive effect on the number of bacteria forming units,with an increase of approximately 385%.On the other hand,no significant positive effect on sugarcane development was ***,biochar application in high-fertility sugarcane plantation soil did not result in gains for sugarcane development in the periods evaluated.

关键词： Soil Biometry Microbiology Double drum oven Biochar

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Late diagnosis and TCD8 immune response profile of cutaneous tuberculosis: A case report

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Open Journal of Immunology 2012年第3期2卷 125-131页

作者： bruna Daniella de Souza Silva Sueli Lemes de ávila alves André Kipnis Ana Paula Junqueira-Kipnis Departamento de Microbiologia Imunologia Patologia e Parasitologia Instituto de Patologia Tropical e Saúde Pública Universidade Federal de Goiás Goiania/GO Brazil Laboratório Central de Saúde Pública Dr. Giovanni Cysneiros LACEN/GO Goiania/GO Brazil

Introduction: Cutaneous tuberculosis (CTB) is a rare form of extra-pulmonary tuberculosis that, when associated with late diagnosis, worsen the quality of life of the sick individuals. This report presents a case of late diagnosis of CTB. Unusual clinical manifestations retarded the correct tuberculosis diagnosis for more than a year. The immune response elicited by this type of tuberculosis as well as the factors that might contribute to the delay in diagnosis was evaluated and discussed. Methodology: Clinical evaluation and flow cytometric analyses of PBMC were realized for a case of CTB and a healthy individual as a control. Results: M. tuberculosis specific TCD8+ cell response was analyzed by flow cytometry and revealed positive cells for IL-17, IL-10, TGF-β and IDO. The CTB patient presented higher percentage of those cells when compared to a healthy donor. However, TCD8 cells positive for the important protective cytokine, IFN-γ was decreased in the CTB patient. Conclusion. The assessment of the M. tuberculosis specific TCD8+ immune response showed a regulatory/modulatory phenotype with a reduced IFN-γ response when compared to the healthy control that could have contributed to the CTB infection.

关键词： Cutaneous tuberculosis Late Diagnosis CD8+ T Cells

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The Ethics and the Meaning of Life among College Students

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International Journal of Clinical Medicine 2018年第4期9卷 221-233页

作者： Maria Helena de Agrela Goncalves Jardim Geraldo Bezerra da Silva Junior Marcia Lucia Sousa Dias alves bruna Raquel Figueira Ornelas de Gouveia Rita Baptista Silva School of Health University of MadeiraFunchalPortugal Visiting Researcher at UNIFOR by Capes/Funcap FortalezaBrazil Health Sciences Center University of FortalezaFortalezaBrazil Hospital of Dr.Nelio Mendonca MadeiraPortugal Abel Salazar Biomedical Sciences Institute University of PortoPortoPortugal 6School of Nursing of Sao Jose de ClunnyFunchalPortugal Nursing Sciences University of PortoPortoPortugal

The concern of the ethics and the meaning of life in young adults became universal and are present in all contexts of human life. Such universality is due to the development of modern rationality, to establish a relationship between the intrinsic theoretical dimensions (scientific) and practical dimensions (ethical), originated that are present in the own array of knowledge. This descriptive cross-sectional study, aims to identify the values of the ethical dimension and meaning of life defended by the college students of the Universities of Madeira, Portugal and Fortaleza, Brazil. The sample consists of 605 University students (Madeira = 225 and Fortaleza = 380), with an average age of 21 years and a standard deviation of 2. We used the questionnaire on values (adapted from the European Values Survey). Most of the young people referred to have a religion (60% wood and 78.4% stronghold), being the most Catholic, however, present in your frequency disinterest and, yet, in Brazil there is a greater diversity of religions. Supporting the intervention of religious institutions in situations of everyday life is accepted mostly by Brazilians, with the exception of politics (35.5%). On the other hand, the university students of the University of Madeira understand that Religious Institutions should only give their opinion on racial discrimination (76.6%). Believe in God (90.8% and 55.1% Stronghold) and Soul (80.3% and 66.4% Stronghold) are beliefs more referred to by college students. These results are intended to contribute in the field of research on ethical values and meaning of life in young people. This study contributes to future comparative research among university students and to developing strategic programs in education and health, increasing the success and excellence in the formation of a full citizenship, preventing the fanaticisms and the social discrimination that today devastate the collective globally.

关键词： Values Ethics Meaning of Life Young Adults College Students Questionnaire on Values (QSV)

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<i>Conyza sumatrensis</i>Intrapopulation Variation in Response to Glufosinate

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American Journal of Plant Sciences 2019年第9期10卷 1565-1582页

作者： Ivana Paula Ferraz Santos de Brito Caio Antonio Carbonari bruna Barboza Marchesi Ana Karollyna alves de Matos Leandro Tropaldi Nilda Roma-Burgos Edivaldo Domingues Velini Department of Crop Science Sao Paulo State University (UNESP) College of Agriculture Botucatu Sao Paulo Brazil Department of Crop Soil and Environmental Sciences University of Arkansas Fayetteville AR USA

We aimed to study the response of Conyza sumatrensis to different doses of glufosinate, intrapopulation variation in sensitivity to the herbicide, and the heritability of phenotypic response, and model the evolution of resistance. Three studies were conducted in the greenhouse with two repetitions. First, we tested doses of glufosinate (0, 50, 100, 200, 400, 800 g a.i. ha-1) plus a nontreated check, with four replications. Second, we examined the range in sensitivity of 44 plants to 200 g a.i. ha-1 glufosinate. Third, we evaluated the sensitivity of the progeny of six glufosinate-treated plants to 200 g a.i. ha-1 glufosinate. Plant response was evaluated visually and the ammonium content in leaf tissues was measured. Glufosinate at 400 g a.i. ha-1 caused the highest injury to *** plants. Ammonia accumulation occurred in response to glufosinate treatment, regardless of dose. Ammonia accumulation was correlated strongly with the level of visible plant injury;thus, it is a good indicator of herbicide efficacy. Sensitivity to glufosinate was highly variable within the population. Plants with high ammonia concentration (high injury) after treatment with glufosinate produced progenies that also had high ammonia concentrations after herbicide treatment. The variation in ammonia accumulation among siblings was high. Simulating the exclusion of plants that accumulated more ammonia produced a population that is expected to be less sensitive to glufosinate in the next generation. The stronger the selection pressures by a simulated treatment with glufosinate, the greater the reduction in ammonia accumulation in the progeny and expected sensitivity to glufosinate.

关键词： Ammonia Accumulation Differential Tolerance Glutamine Synthetase Herbicide Selection Pressure Sumatran Fleabane

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Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts

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Infectious Diseases of Poverty 2020年第6期9卷 5-15页

作者： Pedro Henrique Ferreira Marçal Rafael Silva Gama Lorena bruna Pereira de Oliveira Olindo Assis Martins-Filho Roberta Olmo Pinheiro Euzenir Nunes Sarno Milton Ozório Moraes Lucia alves de Oliveira Fraga Universidade Vale do Rio Doce–Univale Governador ValadaresMGBrazil Grupo Integrado de Pesquisas em Biomarcadores Institute Rene RachouFIOCRUZ-MinasBelo HorizonteMGBrazil Laboratorio de Hanseniase Instituto Oswaldo CruzFundagao Oswaldo Cruz-FIOCRUZ-RJRio de JaneiroRJBrazil Nucleo de Pesquisa em Hansenologia Universidade Federal de Juiz de ForaInstituto de Ciencias da VidaCam pus Governador ValadaresRua Sao Paulo582-CentroGovernador ValadaresMG 30190-002Brazil

Background: Leprosy is a chronic infectious disease classified into two subgroups for therapeutic purposes:paucibacillary(PB)and multibacillary(MB),closely related to the host immune *** this context it is noteworthy looking for immunological biomarkers applicable as complementary diagnostic tools as well as a laboratorial strategy to follow-up leprosy household ***:: The cross-sectional study enrolled 49 participants,including 19 patients and 30 healthy *** blood mononuclear cells(PBMC)were isolated and incubated in the presence of Mycobacterium leprae *** cells were prepared for surface(CD4+and CD8+)and intracytoplasmic cytokine staining(IFN-γ,IL-4 and IL-10).Multiple comparisons amongst groups were carried out by ANOVA,Kruskal–Wallis,Student T or Mann–Whitney *** analysis of categorical variables was performed by *** biomarker signature analysis was conducted using the global median values for each biomarker index as the cut-off edge to identify the proportion of subjects with high biomarker ***: The cytokine signature analysis demonstrated that leprosy patients presented a polyfunctional profile of T-cells subsets,with increased frequency of IFN-γ+T-cell subsets along with IL-10+and IL-4+from CD4+T-cells,as compared to health Controls(Venn diagram report).Moreover,statistical analysis was carried out using parametric or non-parametric variance analysis followed by pairwise multiple comparisons,according to the data normality distribution.L(PB)displayed a polyfunctional profile characterized by enhanced percentage of IFN-γ+,IL-10+and IL-4+produced by most T-cell subsets,as compared to L(MB)that presented a more restricted cytokine functional profile mediated by IL-10+and IL-4+T-cells with minor contribution of IFN-γproduced by CD4+*** was that HHC(MB)exhibited enhanced frequency of IFN-γ+T-cells,contrasting with HHC(PB)that presented a cytokine profile limited t

关键词： Leprosy Mycobacterium leprae Cytokines Household contacts

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Encapsulation of phenolic compounds through the complex coacervation technique for the enrichment of diet chewable candies

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Food Bioscience 2023年第1期51卷 325-334页

作者： Lisiane Pintanela Vergara Helen Cristina dos Santos Hackbart Cristina Jansen alves Gabriela Niemeyer Reissig bruna Santos Wachholz Caroline Dellinghausen Borges Josiane Freitas Chim Rui Carlos Zambiazi Department of Agroindustrial Science and Technology Federal University of PelotasPelotasRSBrazil Federal Institute of Rio Grande do Sul Campus CAVGPelotasRSBrazil Laboratory of Plant Cognition and Electrophysiology Department of BotanyInstitute of BiologyFederal University of PelotasPelotasRSBrazil Center of Chemical Pharmaceutical and Food SciencesFederal University of PelotasPelotasRSBrazil

The aim of this study was to encapsulate blackberry juice through complex coacervation,using carrageenan,tragacanth,and xanthan associated with pea protein as wall materials,in addition to characterizing the particles and evaluating the profile of release in vitro after its application in diet chewable candies with blended pulp of blackberry,butia and red *** following analyses were performed:phenolic compounds,turbidimetry,encapsulation efficiency,antioxidant activity,morphology(SEM),functional groups(FTIR),thermal behavior(DSC),and in vitro *** complex coacervation between pea protein/carrageenan,pea protein/tragacanth,and pea protein/xanthan particles occurred at pH 3.09,4.61,and 3.45 respectively,in a ratio of 1:2(w/w).Higher values of encapsulation efficiency and antioxidant activity were observed for pea protein/carrageenan and pea protein/*** and FTIR analyses confirmed the *** application of pea protein/tragacanth particles in the production of candies proved to be efficient for providing the highest percentages of phenolic compound release in the intestinal phase.

关键词： Pea protein Carrageenan gum Tragacanth gum Xanthan gum In vitro digestion Blackberry juice

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Transcranial direct current electrical stimulation in combination with aerobic exercise:A pilot study in post-COVID-19 systemic autoimmune rheumatic patients

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World Journal of Rheumatology 2023年第1期11卷 1-12页

作者： Rafael Giovani Missé Alexandre Moura dos Santos Isabela bruna Pires Borges Marlise Sítima Mendes Simões Lorenza Rosa Silvério bruna Lindoso Correia Ana Wook Sook Kim Aline Marques Caetano Sandra Gofinet Pasoto Carla Gonçalves Schahin Saad Diogo Souza Domiciano Clarice Tanaka Julia Maria D’Andrea Greve Abrahão Fontes Baptista Samuel Katsuyuki Shinjo Division of Rheumatology Hospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de Sao PauloSao PauloBrazil Departamento de Fisioterapia Fonoaudiologia e Terapia OcupacionalHospital das Clínicas HCFMUSPFaculdade de MedicinaUniversidade de Sao PauloNúcleo de Assistência e Pesquisa em NeuromodulaçãoSao PauloBrazil Laboratório de Estudos do Movimento Instituto de Ortopedia e TraumatologiaHospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de Sao PauloSao PauloBrazil

BACKGROUND Systemic autoimmune rheumatic diseases(SARDs)are a group of diseases with multiorgan involvement and a high prevalence of chronic pain and *** with SARDs and post-coronavirus disease 2019(COVID-19)syndrome experience aggravation of *** this context,it is essential to establish strategies to reduce chronic pain and fatigue and improve quality of *** To assess the efficacy of transcranial direct current stimulation(tDCS)for the treatment of fatigue and pain-associated post-COVID-19 syndrome in patients with *** This study included nine patients with different types of *** patients had reverse transcription-polymerase chain reaction(RT-PCR)test confirmed COVID-19 as well as significant,persistent fatigue and pain that began to worsen after *** tDCS was administered in five daily sessions(2mA,20 min).Concomitantly,patients were involved in aerobic exercise *** participants were evaluated using specific questionnaires and strength assessment by handgrip and physical function by timed-up-and-go test and sit-to-stand test at baseline(within one week before tDCS protocol),and one week after tDCS *** all procedures,the patients’treatments remained *** The sample comprised eight women and one man with a mean age of 48.7±9.6 *** the tDCS protocol,pain and fatigue significantly improved on the visual analog scale(P<0.05).The physical function also improved 9.5±2.7 vs 6.8±0.8(P=0.001)for timed-up-go-test and 10.3±3.7 vs 15.1±4.0(P=0.037)for sit-to-stand *** of the patients experienced any adverse *** The present study showed that tDCS in combination with aerobic exercise was effective in improving physical function,and reducing fatigue/pain in SARDs patients with post-COVID-19 syndrome.

关键词： Autoimmune diseases COVID-19 Fatigue Neuromodulation Physical function Rheumatic diseases Pain

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Chemical characterization UPLC-ESI-QToF-MSE,antibacterial and antibiofilm potential of Sarcomphalus joazeiro(MART.)Hauenschild

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Food Bioscience 2022年第6期50卷 1249-1259页

作者： Nara J.S.Araújo Ana Raquel P.Silva Maria S.Costa Thiago S.Freitas José M.Barbosa Filho Yedda M.L.S.Matos Maria Flaviana B.Morais-Braga Francisco N.Pereira Junior C.A.P.Silva Erlânio O.Souza Paulo R.V.Ribeiro bruna Caroline Gonçalves Vasconcelos de Lacerda Edlane Martins de Andrade Henrique D.M.Coutinho Jacqueline C.Andrade-Pinheiro Programa de pós-graduação em Ciências da Saúde Universidade Federal do CaririUFCADivino Salvador284CEP63180-000BarbalhaCEBrazil Programa de pós-graduação em Biotecnologia Universidade Estadual do CearáUECEAv.Dr Munguba1700CEP60714-903FortalezaCEBrazil Departamento de Química Biológica Universidade Regional do CaririURCACel Antônio Luis1161CEP63105-000CratoCEBrazil Laboratório de Tecnologia Farmacêutica Universidade Federal da ParaíbaUFPBCidade Universitária5009CEP58051-970João PessoaPBBrazil Laboratório de Bioensaios – LABIO Universidade Federal do Cariri – UFCAR.Olegário Emidio de Araujos/nCEP63260-000Brejo SantoCEBrazil Faculdade de Tecnologia do Cariri FATECAmália Xavier de OliveiroCEP63040-000Juazeiro do NorteCEBrazil Embrapa Agroindústria Tropical R.Pernambuco2270 - Pici60511-110FortalezaCEBrazil CECAPE College.Av.Padre Cícero 3917 - São JoséJuazeiro do NorteCE63024-015Brazil

The present study aims to demonstrate the chemical composition of the ethanolic extract of Sarcomphalus joazeiro bark and to evaluate its antibacterial and antibiofilm *** that,the ethanolic extract of the stem bark was prepared,and chemical characterization was carried out in *** inhibitory concentration and antibiotic modification test were performed by the microdilution *** and antiformation assays were evaluated by the crystal violet *** the chemical characterization,the presence of 24 peaks was *** activity showed minimum inhibitory concentration≥2048μg/*** the evaluations of the potentiating activity,synergism was the most *** the formation analysis,it was observed that most strains showed moderate biofilm *** was concluded that saponin derivatives are the major secondary metabolites in the analyzed extract and that it presents relevant synergism with the antibiotics studied and a significant ability to inhibit bacterial biofilm formation.

关键词： Biofilm Saponins Synergism Inhibition

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