Pharmacological inhibition of lysine-specific demethylase 1 (LSD1) induces global transcriptional deregulation and ultrastructural alterations that impair viability in Schistosoma mansoni

Treatment and control of schistosomiasis still rely on only one effective drug, praziquantel (PZQ) and, due to mass treatment, the increasing risk of selecting for schistosome strains that are resistant to PZQ has alerted investigators to the urgent need to develop novel therapeutic strategies. The histone-modifying enzymes (HMEs) represent promising targets for the development of epigenetic drugs against Schistosoma mansoni. In the present study, we targeted the S. mansoni lysine-specific demethylase 1 (SmLSD1), a transcriptional corepressor, using a novel and selective synthetic inhibitor, MC3935, which was used to treat schistosomula and adult worms in vitro. By using cell viability assays and optical and electron microscopy, we showed that treatment with MC3935 affected parasite motility, egg-laying, tegument, and cellular organelle structures, culminating in the death of schistosomula and adult worms. In silico molecular modeling and docking analysis suggested that MC3935 binds to the catalytic pocket of SmLSD1. Western blot analysis revealed that MC3935 inhibited SmLSD1 demethylation activity of H3K4me1/2. Knockdown of SmLSD1 by RNAi recapitulated MC3935 phenotypes in adult worms. RNA-Seq analysis of MC3935-treated parasites revealed significant differences in gene expression related to critical biological processes. Collectively, our findings show that SmLSD1 is a promising drug target for the treatment of schistosomiasis and strongly support the further development and in vivo testing of selective schistosome LSD1 inhibitors

Kinetics of mass loss of arabica coffee during roasting process

Roasting is one of the most complex coffee processing steps due to simultaneous transfers of heat and mass. During this process, beans lose mass because of fast physical and chemical changes that will set color and flavor of the commercial coffee beverage. Therefore, we aimed at assessing the kinetics of mass loss in commercially roasted coffee beans according to heating throughout the processing. For that, we used samples of 350-g Arabica coffee processed grains with water content of 0.1217 kga kg-1, in addition to a continuous roaster with firing gas. The roaster had initial temperatures of 285, 325, 345 and 380 °C, decreasing during the process up to 255, 285, 305 and 335 °C respectively. Mass loss was calculated by the difference between grain weight before and after roasting. We observed a linear variation directly dependent on roaster temperature. For each temperature during the process was obtained a constant mass loss rate, which was reported by the Arrhenius model with r2 above 0.98. In a roaster in non-isothermal conditions, the required activation energy to start the mass loss in a commercial coffee roasting index was 52.27 kJ mol -1.A torrefação é uma das etapas mais complexa do processamento do café devido à transferência simultânea de calor e massa, em que os grãos perdem massa devido à rapidez das mudanças físicas e químicas, necessárias para produzir a cor e o aroma do café comercial. Assim, objetivou-se com este trabalho determinar a cinética da perda de massa dos grãos de café torrados comercialmente em função da temperatura do processo. Foram usadas amostras de 350 g de grãos beneficiados de café arábica com teor de água de 0,1217 kga kg-1 . Usou-se um torrador com queima de gás constante e temperaturas iniciais de 285; 325; 345 e 380 °C, que diminuíram durante a operação até equilibrar-se em 255; 285; 305 e 335 °C, respectivamente. A perda de massa foi calculada a partir do peso dos grãos antes e depois da torração, sendo observada uma variação linear dependente diretamente da temperatura do torrador. Para cada temperatura do processo, foi obtida uma taxa constante de perda de massa, que foi relacionada pelo modelo de Arrhenius com r2 acima de 0,98. Em condições não isotérmicas do torrador, a energia de ativação necessária para iniciar a perda de massa, em índices de torração comercial do café, foi 52,27 kJ mol-1 .Universidad de Costa Rica/[]/UCR/Costa RicaConselho Nacional de Desenvolvimento Científico e Tecnológico/[]/CNPq/BrasilCoordenação de Aperfeiçoamento de Pessoal de Nível Superior/[]/CAPES/ BrasilFundação de Amparo à Pesquisa do Estado de Minas Gerais/[]/FAPEMIG/BrasilUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Centro para Investigaciones en Granos y Semillas (CIGRAS

First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR)

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an 'overarching' treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.Fil: Pons Estel, Bernardo A.. Centro Regional de Enfermedades Autoinmunes y Reumáticas; ArgentinaFil: Bonfa, Eloisa. Universidade de Sao Paulo; BrasilFil: Soriano, Enrique R.. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Cardiel, Mario H.. Centro de Investigación Clínica de Morelia; MéxicoFil: Izcovich, Ariel. Hospital Alemán; ArgentinaFil: Popoff, Federico. Hospital Aleman; ArgentinaFil: Criniti, Juan M.. Hospital Alemán; ArgentinaFil: Vásquez, Gloria. Universidad de Antioquia; ColombiaFil: Massardo, Loreto. Universidad San Sebastián; ChileFil: Duarte, Margarita. Hospital de Clínicas; ParaguayFil: Barile Fabris, Leonor A.. Hospital Angeles del Pedregal; MéxicoFil: García, Mercedes A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Amigo, Mary Carmen. Centro Médico Abc; MéxicoFil: Espada, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Catoggio, Luis J.. Hospital Italiano. Instituto Universitario. Escuela de Medicina; ArgentinaFil: Sato, Emilia Inoue. Universidade Federal de Sao Paulo; BrasilFil: Levy, Roger A.. Universidade do Estado de Rio do Janeiro; BrasilFil: Acevedo Vásquez, Eduardo M.. Universidad Nacional Mayor de San Marcos; PerúFil: Chacón Díaz, Rosa. Policlínica Méndez Gimón; VenezuelaFil: Galarza Maldonado, Claudio M.. Corporación Médica Monte Sinaí; EcuadorFil: Iglesias Gamarra, Antonio J.. Universidad Nacional de Colombia; ColombiaFil: Molina, José Fernando. Centro Integral de Reumatología; ColombiaFil: Neira, Oscar. Universidad de Chile; ChileFil: Silva, Clóvis A.. Universidade de Sao Paulo; BrasilFil: Vargas Peña, Andrea. Hospital Pasteur Montevideo; UruguayFil: Gómez Puerta, José A.. Hospital Clinic Barcelona; EspañaFil: Scolnik, Marina. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Pons Estel, Guillermo J.. Centro Regional de Enfermedades Autoinmunes y Reumáticas; Argentina. Hospital Provincial de Rosario; ArgentinaFil: Ugolini Lopes, Michelle R.. Universidade de Sao Paulo; BrasilFil: Savio, Verónica. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Drenkard, Cristina. University of Emory; Estados UnidosFil: Alvarellos, Alejandro J.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Ugarte Gil, Manuel F.. Universidad Cientifica del Sur; Perú. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Babini, Alejandra. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Cavalcanti, André. Universidade Federal de Pernambuco; BrasilFil: Cardoso Linhares, Fernanda Athayde. Hospital Pasteur Montevideo; UruguayFil: Haye Salinas, Maria Jezabel. Hospital Privado Universitario de Córdoba; ArgentinaFil: Fuentes Silva, Yurilis J.. Universidad de Oriente - Núcleo Bolívar; VenezuelaFil: Montandon De Oliveira E Silva, Ana Carolina. Universidade Federal de Goiás; BrasilFil: Eraso Garnica, Ruth M.. Universidad de Antioquia; ColombiaFil: Herrera Uribe, Sebastián. Hospital General de Medellin Luz Castro de Gutiérrez; ColombiaFil: Gómez Martín, DIana. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Robaina Sevrini, Ricardo. Universidad de la República; UruguayFil: Quintana, Rosana M.. Hospital Provincial de Rosario; Argentina. Centro Regional de Enfermedades Autoinmunes y Reumáticas; ArgentinaFil: Gordon, Sergio. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Fragoso Loyo, Hilda. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Rosario, Violeta. Hospital Docente Padre Billini; República DominicanaFil: Saurit, Verónica. Hospital Privado Universitario de Córdoba; ArgentinaFil: Appenzeller, Simone. Universidade Estadual de Campinas; BrasilFil: Dos Reis Neto, Edgard Torres. Universidade Federal de Sao Paulo; BrasilFil: Cieza, Jorge. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: González Naranjo, Luis A.. Universidad de Antioquia; ColombiaFil: González Bello, Yelitza C.. Ceibac; MéxicoFil: Collado, María Victoria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Sarano, Judith. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Retamozo, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Sattler, María E.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Gamboa Cárdenas, Rocio V.. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Cairoli, Ernesto. Universidad de la República; UruguayFil: Conti, Silvana M.. Hospital Provincial de Rosario; ArgentinaFil: Amezcua Guerra, Luis M.. Instituto Nacional de Cardiologia Ignacio Chavez; MéxicoFil: Silveira, Luis H.. Instituto Nacional de Cardiologia Ignacio Chavez; MéxicoFil: Borba, Eduardo F.. Universidade de Sao Paulo; BrasilFil: Pera, Mariana A.. Hospital Interzonal General de Agudos General San Martín; ArgentinaFil: Alba Moreyra, Paula B.. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Arturi, Valeria. Hospital Interzonal General de Agudos General San Martín; ArgentinaFil: Berbotto, Guillermo A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Gerling, Cristian. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Gobbi, Carla Andrea. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gervasoni, Viviana L.. Hospital Provincial de Rosario; ArgentinaFil: Scherbarth, Hugo R.. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Brenol, João C. Tavares. Hospital de Clinicas de Porto Alegre; BrasilFil: Cavalcanti, Fernando. Universidade Federal de Pernambuco; BrasilFil: Costallat, Lilian T. Lavras. Universidade Estadual de Campinas; BrasilFil: Da Silva, Nilzio A.. Universidade Federal de Goiás; BrasilFil: Monticielo, Odirlei A.. Hospital de Clinicas de Porto Alegre; BrasilFil: Seguro, Luciana Parente Costa. Universidade de Sao Paulo; BrasilFil: Xavier, Ricardo M.. Hospital de Clinicas de Porto Alegre; BrasilFil: Llanos, Carolina. Universidad Católica de Chile; ChileFil: Montúfar Guardado, Rubén A.. Instituto Salvadoreño de la Seguridad Social; El SalvadorFil: Garcia De La Torre, Ignacio. Hospital General de Occidente; MéxicoFil: Pineda, Carlos. Instituto Nacional de Rehabilitación; MéxicoFil: Portela Hernández, Margarita. Umae Hospital de Especialidades Centro Medico Nacional Siglo Xxi; MéxicoFil: Danza, Alvaro. Hospital Pasteur Montevideo; UruguayFil: Guibert Toledano, Marlene. Medical-surgical Research Center; CubaFil: Reyes, Gil Llerena. Medical-surgical Research Center; CubaFil: Acosta Colman, Maria Isabel. Hospital de Clínicas; ParaguayFil: Aquino, Alicia M.. Hospital de Clínicas; ParaguayFil: Mora Trujillo, Claudia S.. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: Muñoz Louis, Roberto. Hospital Docente Padre Billini; República DominicanaFil: García Valladares, Ignacio. Centro de Estudios de Investigación Básica y Clínica; MéxicoFil: Orozco, María Celeste. Instituto de Rehabilitación Psicofísica; ArgentinaFil: Burgos, Paula I.. Pontificia Universidad Católica de Chile; ChileFil: Betancur, Graciela V.. Instituto de Rehabilitación Psicofísica; ArgentinaFil: Alarcón, Graciela S.. Universidad Peruana Cayetano Heredia; Perú. University of Alabama at Birmingahm; Estados Unido