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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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Biliary tract reconstruction using jejunal tube:an experimental study in dogs

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Hepatobiliary & Pancreatic Diseases International 2009年第2期8卷 179-185页

作者： Eliane Anrain Trentini Eduardo Crema juan Carlos Llanos Mauro Masson Lerco luiz Alberto Magna luiz Sergio Leonardi State University of Campinas Faculty of Medical SciencesDepartment of Surgery Federal University of Triangulo Mineiro So Paulo State University "Júlio de Mesquita Filho" Faculty of Medicine of BotucatuDepartment of Surgery and Orthopedics

BACKGROUND:To physiologically reconstruct the biliary tract,Crema et al suggested the application of the Monti principle to the biliary tract,already used in humans for the urinary *** this technique,a jejunal segment is transversely *** study aimed to evaluate the efficacy of jejunal tube interposition between the common bile duct and duodenum in ***:Thirteen dogs underwent a laparoscopic common bile duct ligature,followed by a biliodigestive connection by jejunal tube interposition after one *** levels of glutamic-pyruvic and glutamic-oxalacetic transaminases,total bilirubins,alkaline phosphatase and gamma-glutamyltransferase were assessed before surgery and thereafter weekly until euthanasia,which was performed 6 weeks after biliodigestive ***:Data on 9 dogs were analyzed *** dogs presented with obstructive jaundice after common bile duct ligature,as confirmed by biochemical *** showed a statistically significant reduction in cholestasis after biliodigestive connection by jejunal tube interposition and were healthy until the end of the ***:A statistically significant reduction was seen in total bilirubin and canalicular enzymes(alkaline phosphatase and gamma-glutamyltransferase)in the 9 dogs 6 weeks after biliodigestive connetion by jejunal tube interposition.

关键词： biliary tract surgical procedures monti principle obstructive jaundice

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Evaluating seroprevalence to circumsporozoite protein to estimate exposure to three species of Plasmodium in the Brazilian Amazon

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Infectious Diseases of Poverty 2018年第1期7卷 448-459页

作者： Virginia Araujo Pereira juan Camilo Sanchez-Arcila Mariana Pinheiro Alves Vasconcelos Amanda Ribeiro Ferreira Lorene de Souza Videira Antonio Teva Daiana Perce-da-silva Maria Teresa Queiroz Marques Luzia Helena de Carvalho Dalma Maria Banic luiz Cristovao Sobrino Porto Joseli Oliveira-Ferreira Laboratory of Immunoparasitology Oswaldo Cruz Institute/FiocruzAv.Brasil 4365ManguinhosRio de JaneiroBrazil Institute of Infectology Emilio Ribas São PauloSao PauloBrazil Laboratory of Immunodiagnosis Departament of Biological SciencesNational School of Public Health/FiocruzRio de JaneiroBrazil Laboratory of Clinical Immunology Oswaldo Cruz Institute/FiocruzRio de JaneiroBrazil Laboratory of Histocompatibility and Cryopreservation–HLA of DHE/IBRAG/UERJ Rio de JaneiroBrazil Molecular Biology and Malaria Immunology Research Group Centro de Pesquisas Rene Rachou/FiocruzBelo HorizonteMinas GeraisBrazil

Background:Brazil has seen a great decline in malaria and the country is moving towards ***,for eventual elimination,the control program needs efficient tools in order to monitor malaria exposure and *** this study,we aimed to evaluate whether seroprevalence to the circumsporozoite protein(CSP)is a good tool for monitoring the exposure to and/or evaluating the burden and distribution of Plasmodium species in the Brazilian ***:Cross-sectional surveys were conducted in a rural area of Porto Velho,Rondônia *** infection was detected by microscopy and polymerase chain *** to the sporozoite CSP repeats of Plasmodium vivax,***,and ***(PvCS,PfCS,and PmCS)were detected using the enzyme-linked immunosorbent assay *** leukocyte antigen(HLA)-DRB1 and DQB1 genes were typed using Luminex®xMAP®***:The prevalence of immunoglobulin G against *** CSP peptide(62%)was higher than ***(49%)and ***(46%)CSP *** of the studied individuals had antibodies to at least one of the three peptides(72%),34%had antibodies to all three peptides and 28%were *** the majority of the population was not infected at the time of the survey,74.3%of parasite-negative individuals had antibodies to at least one of the ***,among individuals carrying the haplotypes DRB1*04~DQB1*03,there was a significantly higher frequency of PfCS responders,and DRB1*16~DQB1*03 haplotype for PvCS and PfCS *** contrast,HLA-DRB1*01 and HLA-DQB1*05 allelic groups were associated with a lack of antibodies to *** and *** CSP repeats,and the haplotype DRB1*01~DQB1*05 was also associated with non-responders,including non-responders to ***:Our results show that in low transmission settings,naturally acquired antibody responses against the CSP repeats of ***,***,and *** in a single cross-sectional study may n

关键词： Malaria Circumsporozoite protein Serological marker Human leucocyte antigen IgG antibody Porto Velho Rondônia Brazil

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Characterization and Evaluation of Bond Strength of Dental Polymer Systems Modified with Hydroxyapatite Nanoparticles

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Journal of Materials Science and Chemical Engineering 2013年第7期1卷 13-23页

作者： Vitor César Dumont Rafael Menezes silva luiz Edmundo Almeida-Júnior juan Pedro Bretas Roa Adriana Maria Botelho Maria Helena Santos Department of Dentistry Federal University of Vales do Jequitinhonha and Mucuri Diamantina Brazil Department of Dentistry Federal University of Vales do Jequitinhonha and Mucuri Diamantina Brazil Advanced Biomaterial Center-BioMat UFVJM Diamantina Brazil Department of Dentistry Federal University of Vales do Jequitinhonha and Mucuri Diamantina Brazil Advanced Biomaterial Center-BioMat UFVJM Diamantina Brazil Institute of Science and Technology UFVJM Diamantina Brazil

The study modifies an adhesive system with hydroxyapatite nanoparticles as load, characterizing it and evaluate the effectiveness of its bond to dental structure. The middle thirds of healthy premolar tooth crowns were obtained, and each crown was sectioned vertically, resulting in two sections. The sections were divided into ten groups (n = 15), in which resin composite restorations were simulated: (G1E and G1D) conventional adhesive system (SAC);(G2E and G2D) SAC modified with HAP;(G3E and G3D) Primer modified with HAP;(G4E and G4D) monocomponent adhesive system;(G5E and G5D) self-etching adhesive system. The specimens were submitted to the microshear test and characterization technique. There was statistically significant difference (Kruskal-Wallis) between the groups (p 0.01). G3 presented the highest bond strength to enamel (64.40 MPa, ±7.36) and dentin (39.59 MPa, ±21.46). The majority of specimens were found adhesive fractures. Bond strength to enamel and dentin of the primer modified with HAP of SAC showed higher values.

关键词： Nanostructures Composites Mechanical Properties Fracture

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Relevant Aspects of Expert Interest in the Perception of the Facial Aesthetic Damage

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Forensic Medicine and Anatomy Research 2020年第1期8卷 1-10页

作者： luiz Eugênio Nigro Mazzilli Nelson Massanobu Sakaguti Mário Marques Fernandes juan Antonio Cobo Plana Fernanda Capurucho Horta Bouchardet Rogério Nogueira de Oliveira Forensic Dentistry Department of Social Dentistry University of São Paulo São Paulo Brazil Institute of Legal Medicine Zaragoza Spain

Forensic aesthetic facial damage—AFD expert’s valuation is a concerning matter in court as expressively vary in between experts. In fact, differences can be quite significant suggesting examiners age, sex and professional qualification may influence this valuation. Aiming to offer a systematic and more objective evaluation, some methods for assessing AFD had been proposed lately. Known as Aesthetic Impairment Impact Perception (AIPE), Cobo-Plana’s revised methodology (2010) was idealized to minimize the examiner’s subjectivity by means of answering an ordered sequence of questions related to the specific damage perception. This research aims to access AFD perception differences (simulated cases) in between Lawyers, Heath professionals (Physicians and Dental surgeons) and general professionals (laypeople) under AIPE methodology in order to allow a better comprehension of AFD when dealing with forensic expertise cases. Within Groups perceptions varied (p < 0.05) when evaluating lesions below “important” severity grade. Raters over 35 Years age scored higher AFD lesions, and rater’s sex (as an independent variable) did not express any significant difference in AFD scoring. The tendency of under-rating AFD lesions below very important severity grade was observed being a matter of major concern considered their prevalence and the effective consequences involved to the victim. These results recommend extra caution when performing AFD evaluation and consequently expertise reports, claiming a more judicious analysis based on consolidated standards and suggest, examiners to be more perceptive to physical damage evaluation in order to include social perceptions and reactions, mainly, victims feelings and constrains over their aesthetic loss.

关键词： Aesthetic Facial Damage Aesthetic Facial Damage Society

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Amniotic membrane as a potent source of stem cells and a matrix for engineering heart tissue

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Journal of Biomedical Science and Engineering 2013年第12期6卷 1178-1185页

作者： Julio Cesar Francisco Ricardo Correa Cunha Rossana Baggio Simeoni luiz Cesar Guarita-Souza Reginaldo Justino Ferreira Ana Carolina Irioda Carolina Maria C.Oliveira Souza Garikipati Venkata Naga Srikanth Soniya Nityanand juan Carlos Chachques Katherine Athayde Teixeira de Carvalho Bioprocess Engineering and Biotechnology Department Federal University of ParanáCuritibaBrazil Cell Therapy and Biotechnology in Regenerative Medicine Research Group Pele Pequeno Príncipe InstituteCuritibaBrazil Experimental Laboratory of Institute of Biological and Health Sciences Pontificial Catholic University of Paraná(PUCPR)Rua Imaculada ConceicaoCuritibaBrazil Federal University of Technology CuritibaBrazil Department of Hematology Stem Cell Research FacultySanjay Gandhi Post-Graduate Institute of Medical SciencesLucknowIndia Laboratory of Biosurgical Research Pompidou HospitalUniversity of Paris DescartesParisFrance

Existing therapies for the treatment of chronic heart failure still have some limitations and there is a pressing need for the development of new therapeutic modalities. The amniotic membrane has been used for the treatment of various diseases, such as conjunctive defects;however, the mechanisms behind its repair functions are still unclear. Regenerative medicine is seeking newer alternatives and among them, biomaterials have emerged in recent years for developing and manipulating molecules, cells, tissues or organs grown in laboratories in order to replace human body parts. Many such materials have been used for this purpose, either synthetically or biologically, in order to provide new medical devices. This review provides a wider view of the regeneration potential of the use of amniotic membrane as a potential biomaterial to facilitate the implementation of new research in surgical procedures. Amniotic membrane appears to be an alternative source of stem cells as well as an excellent biomaterial for cell-based therapeutic applications in engineering heart tissue.

关键词： Amniotic Membrane Heart Tissue Engineering Stem Cells

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Physicochemical Properties of Pyrolysis Bio-Oil from Sugarcane Straw and Sugarcane in Natura

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Journal of Biomaterials and Nanobiotechnology 2013年第2期4卷 10-19页

作者： Josilaine A. C. Durange Margareth R. L. Santos Marcelo M. Pereira luiz A. P. Fernandes Jr. Marcio N. Souza Anderson N. Mendes Liena M. Mesa Caio G. Sánchez Elisabete M. S. Sanchez juan M. M. Pérez Nakédia M. F. Carvalho Escola de Química Universidade Federal do Rio de Janeiro (UFRJ) Rio de Janeiro Brazil Faculdade de Engenharia Agrícola Universidade Estadual de Campinas (UNICAMP) Campinas Brazil Faculdade de Engenharia Mecanica Universidade Estadual de Campinas (UNICAMP) Campinas Brazi Faculdade de Engenharia Mecanica Universidade Estadual de Campinas (UNICAMP) Campinas Brazil Instituto de Química Universidade do Estado do Rio de Janeiro (UERJ) Rio de Janeiro Brazil. Instituto de Química Universidade Federal do Rio de Janeiro (UFRJ) Rio de Janeiro Brazil

Under the renewable energy context, sugarcane biomass pyrolysis has been growing as a convenient route to produce bio-oil, which can be set into the chemical industry and refineries as building blocks or combustion fuel. In this work sugarcane straw was submitted to direct pyrolysis in a fluidized bed pilot plant at 500°C, in presence of air. Sugarcane in natura was also pyrolysed as a model for comparison, in order to determine the viability of processing different sources of raw biomass. The physicochemical characterization of the biomass precursors as well as of the bio-oils was also carried out, which points both biomass feedstocks as suitable for bio-oil production in terms of viscosity, surface tension, density and acidity. The bio-oil obtained from sugarcane in natura presented higher carbon and hydrogen content as well as lower oxygen content. On the other hand, the metal content is higher in the bio-oil obtained from sugarcane straw, in special the iron and potassium contents were 807 ppm and 123 ppm against 27 ppm and 1 ppm in the bio-oil from sugarcane in natura. Aliphatic and aromatic compounds as well as carbohydrates scaffolds were identified as the main components of the bio-oil. GC-MS analyses showed aromatic products from lignine fragmentation and free sugars and sugar derivatives.

关键词： Sugarcane Pyrolysis Bio-Oil Characterization

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