Protective effect of n-acetyl-L-cysteine and rosuvastatin against oxidative stress in fibroblasts from asymptomatic patients with X-ALD: a preliminary study

Introduction: Several studies in the literature have evaluated the role of oxidative stress and adjuvant therapies for X-linked adrenoleukodystrophy (X-ALD). Here, we investigated whether n-acetyl-L-cysteine (NAC) and rosuvastatin (RSV) could influence the generation of reactive species, redox status and nitrative stress in fibroblasts from asymptomatic patients with X-ALD. Methods: Skin biopsy samples were cultured and treated for 2 hours (37 °C) with NAC and RSV.Results: X-ALD fibroblasts generated high levels of reactive oxygen species. These levels were significantly lower in fibroblasts treated with NAC and RSV relative to untreated samples. The X-ALD fibroblasts from asymptomatic patients also had higher catalase activity, and only NAC was able to increase enzyme activity in the samples.Conclusion: Our results indicated that NAC and RSV were able to improve oxidative stress parameters in fibroblasts from asymptomatic patients with X-ALD, showing that adjuvant antioxidant therapy may be a promising treatment strategy for asymptomatic patients with this disease

Thermal stability and decomposition kinetics of NdNiO3− δ at 1 bar of O2

Despite the interest in rare-earth nickelates for applications, their processing under 1 bar of oxygen pressure is still challenging. In this work, we report the co-precipitation synthesis, thermal stability and thermally driven decomposition of NdNiO3 phase, in order to determine the synthesis parameters towards a pure perovskite phase. We concluded that using a 1% molar excess of Nd during preparation and posterior annealing at around 900 °C at 1 bar of O2 yields an almost pure NdNiO3−δ phase (with a hexagonal Nd2O3 phase below 0.6% molar), with an oxygen deficiency of δ = 0.082 ± 0.001. The decomposition of the NdNiO3−δ phase into Nd4Ni3O10 and NiO was found to start above 900 °C. On further heating, above 1050 °C, the Nd4Ni3O10 decomposes into Nd2NiO4 and NiO phases. Structural parameters and Raman spectra are provided for the NdNiO3, Nd4Ni3O10 and Nd2NiO4 compounds.The authors would like to acknowledge Fundacao para a Ciencia e Tecnologia (FCT) through projects NORTE/01/0145/FEDER/028538, CERN/FIS-PAR/0005/2017, CERN/FIS-TEC/0003/2019, PTDC/FIS-MAC/29454/2017 and when appropriate co-financed by FEDER under PT2020 Partnership Agreement: CQVR: UIDB/QUI/00616/2020; IFIMUP-IN: Norte-070124-FEDER-000070; NECL: NORTE-01-0145-FEDER-022096, UID/NAN/50024/2019. P. Machado and J. Oliveira acknowledge FCT through Ph.D. Grants SFRH/BD/108509/2015 and SFRH/BD/146886/2019 respectively. A special acknowledgment is made to CEMUP for XPS measurements

Co-Administration of a Plasmid DNA Encoding IL-15 Improves Long-Term Protection of a Genetic Vaccine against Trypanosoma cruzi

Background: Immunization of mice with the Trypanosoma cruzi trans-sialidase (TS) gene using plasmid DNA, adenoviral vector, and CpG-adjuvanted protein delivery has proven highly immunogenic and provides protection against acute lethal challenge. However, long-term protection induced by TS DNA vaccines has not been reported. the goal of the present work was to test whether the co-administration of a plasmid encoding IL-15 (pIL-15) could improve the duration of protection achieved through genetic vaccination with plasmid encoding TS (pTS) alone.Methodology: We immunized BALB/c mice with pTS in the presence or absence of pIL-15 and studied immune responses [with TS-specific IFN-gamma ELISPOT, serum IgG ELISAs, intracellular cytokine staining (IFN-gamma, TNF-alpha, and IL-2), tetramer staining, and CFSE dilution assays] and protection against lethal systemic challenge at 1 to 6 months post vaccination. Mice receiving pTS alone developed robust TS-specific IFN-gamma responses and survived a lethal challenge given within the first 3 months following immunization. the addition of pIL-15 to pTS vaccination did not significantly alter T cell responses or protection during this early post-vaccination period. However, mice vaccinated with both pTS and pIL-15 challenged 6 months post-vaccination were significantly more protected against lethal T. cruzi challenges than mice vaccinated with pTS alone (P6 months post immunization. Also, these TS-specific T cells were better able to expand after in vitro restimulation.Conclusion: Addition of pIL-15 during genetic vaccination greatly improved long-term T cell survival, memory T cell expansion, and long-term protection against the important human parasite, T. cruzi.National Institutes of HealthFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Millennium Institute for Gene TherapySt Louis Univ, Dept Internal Med, St Louis, MO 63103 USAUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol, Escola Paulista Med, São Paulo, BrazilSt Louis Univ, Dept Mol Microbiol, St Louis, MO 63103 USAUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol, Escola Paulista Med, São Paulo, BrazilNational Institutes of Health: RO1 AI040196CNPq: 420067/2005-1Web of Scienc

Subdominant/Cryptic CD8 T Cell Epitopes Contribute to Resistance against Experimental Infection with a Human Protozoan Parasite

During adaptive immune response, pathogen-specific CD8+ T cells recognize preferentially a small number of epitopes, a phenomenon known as immunodominance. Its biological implications during natural or vaccine-induced immune responses are still unclear. Earlier, we have shown that during experimental infection, the human intracellular pathogen Trypanosoma cruzi restricts the repertoire of CD8+ T cells generating strong immunodominance. We hypothesized that this phenomenon could be a mechanism used by the parasite to reduce the breath and magnitude of the immune response, favoring parasitism, and thus that artificially broadening the T cell repertoire could favor the host. Here, we confirmed our previous observation by showing that CD8+ T cells of H-2a infected mice recognized a single epitope of an immunodominant antigen of the trans-sialidase super-family. In sharp contrast, CD8+ T cells from mice immunized with recombinant genetic vaccines (plasmid DNA and adenovirus) expressing this same T. cruzi antigen recognized, in addition to the immunodominant epitope, two other subdominant epitopes. This unexpected observation allowed us to test the protective role of the immune response to subdominant epitopes. This was accomplished by genetic vaccination of mice with mutated genes that did not express a functional immunodominant epitope. We found that these mice developed immune responses directed solely to the subdominant/cryptic CD8 T cell epitopes and a significant degree of protective immunity against infection mediated by CD8+ T cells. We concluded that artificially broadening the T cell repertoire contributes to host resistance against infection, a finding that has implications for the host-parasite relationship and vaccine development

Conhecendo Unidades de Conservação

Unidades de Conservação (UC) são espaços utilizados mundialmente como parte de estratégias para a proteção de paisagens naturais, ecossistemas, recursos naturais e sua biodiversidade associada. No Brasil, essas áreas são regidas por lei e categorizadas conforme as restrições de uso para atividades humanas. Em função da implementação, gestão e monitoramento da UC, surgem conflitos entre setores da sociedade com distintos interesses de natureza social, ambiental, política e econômica. Tais conflitos muitas vezes resultam do desconhecimento por parte da sociedade a respeito das Unidades de Conservação

Pathogen-Induced Proapoptotic Phenotype and High CD95 (Fas) Expression Accompany a Suboptimal CD8+ T-Cell Response: Reversal by Adenoviral Vaccine

MHC class Ia-restricted CD8+ T cells are important mediators of the adaptive immune response against infections caused by intracellular microorganisms. Whereas antigen-specific effector CD8+ T cells can clear infection caused by intracellular pathogens, in some circumstances, the immune response is suboptimal and the microorganisms survive, causing host death or chronic infection. Here, we explored the cellular and molecular mechanisms that could explain why CD8+ T cell-mediated immunity during infection with the human protozoan parasite Trypanosoma cruzi is not optimal. For that purpose, we compared the CD8+ T-cell mediated immune responses in mice infected with T. cruzi or vaccinated with a recombinant adenovirus expressing an immunodominant parasite antigen. Several functional and phenotypic characteristics of specific CD8+ T cells overlapped. Among few exceptions was an accelerated expansion of the immune response in adenoviral vaccinated mice when compared to infected ones. Also, there was an upregulated expression of the apoptotic-signaling receptor CD95 on the surface of specific T cells from infected mice, which was not observed in the case of adenoviral-vaccinated mice. Most importantly, adenoviral vaccine provided at the time of infection significantly reduced the upregulation of CD95 expression and the proapoptotic phenotype of pathogen-specific CD8+ cells expanded during infection. In parallel, infected adenovirus-vaccinated mice had a stronger CD8 T-cell mediated immune response and survived an otherwise lethal infection. We concluded that a suboptimal CD8+ T-cell response is associated with an upregulation of CD95 expression and a proapoptotic phenotype. Both can be blocked by adenoviral vaccination

OFICINAS DO BRINCAR: UM RESGATE A INFÂNCIA POR MEIO DE JOGOS, BRINQUEDOS E BRINCADEIRAS. (relato de experiência)

A brincadeira e jogo são construções sociais e, portanto culturais. A criança ao nascer está impregnada de práticas estabelecidas nas relações com outros sujeitos, adultos e outras crianças que possibilitam o acesso aos códigos sociais estabelecidos na forma de aprendizagem social. É na brincadeira, na fantasia e posteriormente no jogo com a elaboração de regras mais complexas que a criança se apropria da organização social na qual está inserida. Como processo cultural, o acesso a brincadeira e ao jogo se dá fundamentalmente na relação com outro e com as condições de espaço, materiais e possibilidades de exploração desses elementos. Considerando a importância da brincadeira e do jogo em proposições criativas, de descobertas, elaborações ereelaborações, estamos realizando um projeto de pesquisa denominado “Oficinas do brincar: um resgate a infância por meio de jogos, brinquedos e brincadeiras”, desenvolvido com os acadêmicos da quarta fase do curso de Licenciatura em Pedagogia, do Instituto Federal Catarinense – campi Blumenau (SC), com a perspectiva de propiciar espaço de relacionamento significativo com a brincadeira, o jogo, o brinquedo e práticas corporais expressivas como elementos de acesso a cultura lúdica e, portanto de inserção num contexto social humanizador. A dinâmica do projeto compreende atividades sequenciais com os discentes, semanalmente, nos quais são utilizadas as dependências da própria instituição, que disponibiliza o espaço físico e conta com a colaboração dos estudantes ao trazerem os recursos - como brinquedos, jogos e materiais para práticas corporais e expressivas. O projeto está em fase inicial de desenvolvimento, mas vem confirmando a relevância de seus propósitos, haja visto que parte do princípio de propiciar resgate e vivências da infância, do brincar, através dos jogos, brinquedos e brincadeiras, tematizando discussões em torno da ludicidade, como processo histórico e social, capaz de proporcionar reflexão e colaborar com a formação humana pelo acesso e interação com essas formas de manifestação da cultura. Dessa forma, objetiva-se com esta oficina, propiciar espaço e oportunidades de autoconhecimento, vivências inclusivas, melhora da auto-estima, desenvolver habilidades de comunicação, expressão e interação social dos acadêmicos envolvidos no projeto com os sujeitos participantes, colaborando com a formação acadêmica dos alunos mediadores do projeto tanto no que se refere à prática pedagógica exercida sob a perspectiva de professor, intelectual-pesquisador, bem como para a comunidade envolvida, no sentido de poder recordar os jogos, brinquedos e brincadeiras de suas infâncias por meio de cantos temáticos (num estande ou sala de aula), contendo: mostra do acervo de brinquedos que fizeram parte da infância da turma; produção artesanal de brinquedos sustentáveis com matérias recicláveis; espaço do faz de conta, com oficineiros desenvolvendo atividades recreacionistas para o público visitante