Annona coriacea Mart. fractions promote cell cycle arrest and inhibit autophagic flux in human cervical cancer cell lines

Plant-based compounds are an option to explore and perhaps overcome the limitations of current antitumor treatments. Annona coriacea Mart. is a plant with a broad spectrum of biological activities, but its antitumor activity is still unclear. The purpose of our study was to determine the effects of A. coriacea fractions on a panel of cervical cancer cell lines and a normal keratinocyte cell line. The antitumor effect was investigated in vitro by viability assays, cell cycle, apoptosis, migration, and invasion assays. Intracellular signaling was assessed by Western blot, and major compounds were identified by mass spectrometry. All fractions exhibited a cytotoxic effect on cisplatin-resistant cell lines, SiHa and HeLa. C3 and C5 were significantly more cytotoxic and selective than cisplatin in SiHa and Hela cells. However, in CaSki, a cisplatin-sensitive cell line, the compounds did not demonstrate higher cytotoxicity when compared with cisplatin. Alkaloids and acetogenins were the main compounds identified in the fractions. These fractions also markedly decreased cell proliferation with p21 increase and cell cycle arrest in G2/M. These effects were accompanied by an increase of H2AX phosphorylation levels and DNA damage index. In addition, fractions C3 and C5 promoted p62 accumulation and decrease of LC3II, as well as acid vesicle levels, indicating the inhibition of autophagic flow. These findings suggest that A. coriacea fractions may become effective antineoplastic drugs and highlight the autophagy inhibition properties of these fractions in sensitizing cervical cancer cells to treatment.e FINEP (MCTI/FINEP/MS/SCTIE/DECIT-01/ 2013—FP XII-BIOPLAT), Barretos Cancer Hospital, CAPES, CNPq, FAPEMIG, UFSJ. RMR is a recipient of CNPq Productivity Gran

Coronarin D induces apoptotic cell death and cell cycle arrest in human glioblastoma cell line

Glioblastoma (GBM) is the most frequent and highest–grade brain tumor in adults. The prognosis is still poor despite the use of combined therapy involving maximal surgical resection, radiotherapy, and chemotherapy. The development of more efficient drugs without noticeable side effects is urgent. Coronarin D is a diterpene obtained from the rhizome extract of Hedychium coronarium, classified as a labdane with several biological activities, principally anticancer potential. The aim of the present study was to determine the anti–cancer properties of Coronarin D in the glioblastoma cell line and further elucidate the underlying molecular mechanisms. Coronarin D potently suppressed cell viability in glioblastoma U–251 cell line, and also induced G1 arrest by reducing p21 protein and histone H2AX phosphorylation, leading to DNA damage and apoptosis. Further studies showed that Coronarin D increased the production of reactive oxygen species, lead to mitochondrial membrane potential depolarization, and subsequently activated caspases and ERK phosphorylation, major mechanisms involved in apoptosis. To our knowledge, this is the first analysis referring to this compound on the glioma cell line. These findings highlight the antiproliferative activity of Coronarin D against glioblastoma cell line U–251 and provide a basis for further investigation on its antineoplastic activity on brain cancer.This research was funded by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2014/06636–7 and 2016/06137–6), financiadora de Estudos e Projetos FINEP (MCTI/FINEP/MS/SCTIE/DECIT–01/2013–FPXII–BIOPLAT)

Reactivation of latent HIV-1 in vitro using an ethanolic extract from Euphorbia umbellata (Euphorbiaceae) latex

Euphorbia umbellata (E. umbellata) belongs to Euphorbiaceae family, popularly known as Janauba, and its latex contains a combination of phorbol esters with biological activities described to different cellular protein kinase C (PKC) isoforms. Here, we identified deoxi-phorbol esters present in E. umbellata latex alcoholic extract that are able to increase HIV transcription and reactivate virus from latency models. This activity is probably mediated by NF-kB activation followed by nuclear translocation and binding to the HIV LTR promoter. In addition, E. umbellata latex extract induced the production of pro inflammatory cytokines in vitro in human PBMC cultures. This latex extract also activates latent virus in human PBMCs isolated from HIV positive patients as well as latent SIV in non-human primate primary CD4+ T lymphocytes. Together, these results indicate that the phorbol esters present in E. umbellata latex are promising candidate compounds for future clinical trials for shock and kill therapies to promote HIV cure and eradication.Research and experimental expenses were funded by the grant E26/2015064289 from FAPERJinfo:eu-repo/semantics/publishedVersio

Rights of nursing terchers in the contemporany: analysis from focal group / Direitos dos docentes de enfermagem na contemporaneidade: análise a partir de grupo focal

Objective: to verify the perception of university nursing professors about their labor rights and to discuss these rights in contemporary times. Method: descriptive and exploratory research with a qualitative approach carried out in two public universities located in the city of Rio de Janeiro. Study participants were 14 nursing professors working at two public universities. For data collection, the focus group was used and the data were analyzed in the light of the content analysis technique. Results: three categories emerged: the rights of nursing professors in public universities in the neoliberal context; education as a right for all for the development of Brazil; and labor rights from the perspective of nursing professors: respect for the employment contract. Nursing professors carry out activities aimed at the training of nurses, as well as the production of knowledge and respect for human rights, however, the work of professors in public universities suffers from the intensification of work by the imposed model of productivity. Final Considerations: the need to respect human rights is highlighted, in order to promote quality of life in the context of the teacher's work.Objetivo: verificar la percepción de los profesores universitarios de enfermería sobre sus derechos laborales y discutir esos derechos en la contemporaneidad. Método: investigación descriptiva y exploratoria con enfoque cualitativo realizada en dos universidades públicas ubicadas en la ciudad de Río de Janeiro. Los participantes del estudio fueron 14 profesores de enfermería que trabajaban en dos universidades públicas. Para la recolección de datos se utilizó el grupo focal y los datos fueron analizados a la luz de la técnica de análisis de contenido. Resultados: surgieron tres categorías: los derechos de los profesores de enfermería en las universidades públicas en el contexto neoliberal; la educación como derecho de todos para el desarrollo de Brasil; y derechos laborales en la perspectiva de los profesores de enfermería: respeto al contrato de trabajo. Los profesores de enfermería realizan actividades encaminadas a la formación de enfermeros, así como a la producción de conocimiento y respeto a los derechos humanos, sin embargo, la labor de los profesores en las universidades públicas sufre la intensificación del trabajo por el modelo de productividad impuesto. Consideraciones finales: se destaca la necesidad de respetar los derechos humanos, con el fin de promover la calidad de vida en el contexto del trabajo docente.Objetivo: verificar a percepção dos docentes universitários de enfermagem acerca dos seus direitos laborais e discutir tais direitos na contemporaneidade. Método: pesquisa descritiva e exploratória de abordagem qualitativa realizada em duas universidades públicas situadas no município do Rio de janeiro. Os participantes do estudo foram 14 docentes de enfermagem lotados em duas universidades públicas. Para a coleta de dados foi utilizado o grupo focal e os dados foram analisados à luz da técnica de análise de conteúdo. Resultados: emergiram três categorias: os direitos do docente de enfermagem nas universidades públicas no contexto neoliberal; educação como direito de todos para o desenvolvimento do Brasil; e direitos laborais sob a ótica dos docentes de enfermagem:  respeito ao contrato de trabalho. Os docentes de enfermagem exercem atividades voltadas para a formação de enfermeiros, bem como a produção de conhecimento e respeito aos direitos humanos, todavia, o trabalho de docentes em universidades públicas sofre com a intensificação do trabalho pelo modelo imposto de produtividade. Considerações Finais: destaca-se a necessidade de respeito aos direitos humanos, para a promoção da qualidade de vida  no contexto do trabalho do docente.

IFNG +874T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-γ production

<p>Abstract</p> <p>Background</p> <p>Interferon-gamma is a key cytokine in the protective responses against intracellular pathogens. A single nucleotide polymorphism (SNP) located in the first intron of the human IFN-γ gene can putatively influence the secretion of cytokine with an impact on infection outcome as demonstrated for tuberculosis and other complex diseases. Our aim was to investigate the putative association of IFNG+874T/A SNP with American tegumentary leishmaniasis (ATL) and also the influence of this SNP in the secretion of IFN-γ <it>in vitro</it>.</p> <p>Methods</p> <p>Brazilian ATL patients (78 cutaneous, CL, and 58 mucosal leishmaniasis, ML) and 609 healthy volunteers were evaluated. The genotype of +874 region in the IFN-γ gene was carried out by Amplification Refractory Mutational System (ARMS-PCR). <it>Leishmania</it>-induced IFN-γ production on peripheral blood mononuclear cell (PBMC) culture supernatants was assessed by ELISA.</p> <p>Results</p> <p>There are no differences between +874T/A SNP frequency in cases and controls or in ML versus CL patients. Cutaneous leishmaniasis cases exhibiting AA genotype produced lower levels of IFN-γ than TA/TT genotypes. In mucosal cases, high and low IFN-γ producers were clearly demonstrated but no differences in the cytokine production was observed among the IFNG +874T or A carriers.</p> <p>Conclusion</p> <p>Our results suggest that +874T/A polymorphism was not associated with either susceptibility or severity to leishmaniasis. Despite this, IFNG +874T/A SNP could be involved in the pathogenesis of leishmaniasis by influencing the amount of cytokine released by CL patients, although it could not prevent disease development. On the other hand, it is possible that in ML cases, other potential polymorphic regulatory genes such as TNF-α and IL-10 are also involved thus interfering with IFN-γ secretion.</p

REFLEXÕES SOBRE MEMÓRIA DE TRABALHO E MEMÓRIA ORGANIZACIONAL NO ÂMBITO DA GESTÃO DO CONHECIMENTO

Este artigo tem por objetivo apresentar e desenvolver algumas reflexões sobre as relações entre memória de trabalho (MT) e memória organizacional (MO) na perspectiva da gestão do conhecimento (GC), levandose em conta os conceitos de criação, estruturação e disseminação do conhecimento. Partindo de abordagens teóricas sobre GC, resgatam-se os conceitos de memória individual especialmente o de memória de trabalho para buscar compreender como a MT, no plano pessoal, possibilita a construção da MO, que é decorrência dos processos de aprendizagem organizacional.Palavras-chave: gestão do conhecimento; aprendizagem organizacional; memória de trabalho (MT); memória organizacional (MO)

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets