HIV Exploits Antiviral Host Innate GCN2-ATF4 Signaling for Establishing Viral Replication Early in Infection.

Antiviral innate host defenses against acute viral infections include suppression of host protein synthesis to restrict viral protein production. Less is known about mechanisms by which viral pathogens subvert host antiviral innate responses for establishing their replication and dissemination. We investigated early innate defense against human immunodeficiency virus (HIV) infection and viral evasion by utilizing human CD4+ T cell cultures in vitro and a simian immunodeficiency virus (SIV) model of AIDS in vivo Our data showed that early host innate defense against the viral infection involves GCN2-ATF4 signaling-mediated suppression of global protein synthesis, which is exploited by the virus for supporting its own replication during early viral infection and dissemination in the gut mucosa. Suppression of protein synthesis and induction of protein kinase GCN2-ATF4 signaling were detected in the gut during acute SIV infection. These changes diminished during chronic viral infection. HIV replication induced by serum deprivation in CD4+ T cells was linked to the induction of ATF4 that was recruited to the HIV long terminal repeat (LTR) to promote viral transcription. Experimental inhibition of GCN2-ATF4 signaling either by a specific inhibitor or by amino acid supplementation suppressed the induction of HIV expression. Enhancing ATF4 expression through selenium administration resulted in reactivation of latent HIV in vitro as well as ex vivo in the primary CD4+ T cells isolated from patients receiving suppressive antiretroviral therapy (ART). In summary, HIV/SIV exploits the early host antiviral response through GCN2-ATF4 signaling by utilizing ATF4 for activating the viral LTR transcription to establish initial viral replication and is a potential target for HIV prevention and therapy.IMPORTANCE Understanding how HIV overcomes host antiviral innate defense response in order to establish infection and dissemination is critical for developing prevention and treatment strategies. Most investigations focused on the viral pathogenic mechanisms leading to immune dysfunction following robust viral infection and dissemination. Less is known about mechanisms that enable HIV to establish its presence despite rapid onset of host antiviral innate response. Our novel findings provide insights into the viral strategy that hijacks the host innate response of the suppression of protein biosynthesis to restrict the virus production. The virus leverages transcription factor ATF4 expression during the GCN2-ATF4 signaling response and utilizes it to activate viral transcription through the LTR to support viral transcription and production in both HIV and SIV infections. This unique viral strategy is exploiting the innate response and is distinct from the mechanisms of immune dysfunction after the critical mass of viral loads is generated

PPARα-targeted mitochondrial bioenergetics mediate repair of intestinal barriers at the host-microbe intersection during SIV infection.

Chronic gut inflammatory diseases are associated with disruption of intestinal epithelial barriers and impaired mucosal immunity. HIV-1 (HIV) causes depletion of mucosal CD4+ T cells early in infection and disruption of gut epithelium, resulting in chronic inflammation and immunodeficiency. Although antiretroviral therapy (ART) is effective in suppressing viral replication, it is incapable of restoring the "leaky gut," which poses an impediment for HIV cure efforts. Strategies are needed for rapid repair of the epithelium to protect intestinal microenvironments and immunity in inflamed gut. Using an in vivo nonhuman primate intestinal loop model of HIV/AIDS, we identified the pathogenic mechanism underlying sustained disruption of gut epithelium and explored rapid repair of gut epithelium at the intersection of microbial metabolism. Molecular, immunological, and metabolomic analyses revealed marked loss of peroxisomal proliferator-activated receptor-α (PPARα) signaling, predominant impairment of mitochondrial function, and epithelial disruption both in vivo and in vitro. To elucidate pathways regulating intestinal epithelial integrity, we introduced probiotic Lactobacillus plantarum into Simian immunodeficiency virus (SIV)-inflamed intestinal lumen. Rapid recovery of the epithelium occurred within 5 h of L. plantarum administration, independent of mucosal CD4+ T cell recovery, and in the absence of ART. This intestinal barrier repair was driven by L. plantarum-induced PPARα activation and restoration of mitochondrial structure and fatty acid β-oxidation. Our data highlight the critical role of PPARα at the intersection between microbial metabolism and epithelial repair in virally inflamed gut and as a potential mitochondrial target for restoring gut barriers in other infectious or gut inflammatory diseases

PRODUÇÃO DE MUDAS DE PARICÁ COM ESCÓRIA, INOCULADAS COM FUNGOS MICORRÍZICOS ARBUSCULARES NA REABILITAÇÃO DE ÁREAS DEGRADADAS

ABSTRACT: The mining causes a number of physical impacts to the environment, of the same way the iron production causes impacts, and the main is the generation of large amounts of wastes that cause environmental and visual pollution. One of these wastes to slag, presents the ability to correct the soil acidity. Then this work has the objective of to produce seedlings of paricá(Schizolobium parahyba var. amazonicum (Huber ex Ducke) Barneby) with increasing doses of slag, inoculated with Arbuscular Mycorrhizal Fungi (AMF) to rehabilitate these areas and minimize environmental and visual pollution. The AMF inoculum was produced by cultivating trap with Brachiaria brizantha in a greenhouse. The seedlings were produced with substrate containing soil in the area of ??tailings and slag, inoculated at planting. The slag used in the experiment was obtained from the company SI NOBRAS. The Paricá seeds passed through the process of breaking dormancy. The experimental design was a factorial using a completely randomized design (CRD). The data were processed and evaluated for the test average (t) 1% and 5% and regression. The variables showed significant levels of 1% in slag factor. The plants inoculated with arbuscular mycorrhizal fungi responded positively the doses of slag.   KEY-WORDS: biological supplies, industrial wastes, restoration.RESUMO: A mineração causa uma série de impactos físicos ao meio, da mesma forma a produção de ferro provoca impactos, e o principal é a geração de grande quantidade de resíduos que causam poluição ambiental e visual. Um desses resíduos a escória, apresenta a capacidade de corrigir a acidez dos solos. Assim este trabalho tem o objetivo de produzir mudas de paricá (Schizolobium parahyba var. amazonicum (Huber ex Ducke) Barneby) com doses crescentes de escória, inoculadas com Fungos Micorrízicos Arbusculares (FMAs) para reabilitar essas áreas e minimizar a poluição ambiental e visual. O inóculo de FMAs foi produzido através do cultivo armadilha com Brachiaria brizantha em casa de vegetação. As mudas foram produzidas com substrato contendo solo da área de rejeito e escória, inoculadas no momento da semeadura. A escória utilizada no experimento foi obtida da empresa SI NOBRAS. As sementes de Paricá passaram pelo processo de quebra de dormência. O delineamento experimental empregado foi um fatorial utilizando o delineamento inteiramente casualizado (DIC). Os dados foram processados e avaliados quanto a teste de média (t) a 1% e 5% e regressão. As variáveis mostraram níveis significativos a nível de 1% no fator escória. As plantas inoculadas com fungos micorrízicos arbusculares responderam positivamente as doses de escória. PALAVRAS-CHAVE: insumos biológicos, resíduo industrial, restabelecimento

PRODUÇÃO DE MUDAS DE ESPÉCIES ARBÓREAS INOCULADAS COM FUNGOS MICORRÍZICOS PARA ATUAR NA REABILITAÇÃO DE ÁREAS IMPACTADAS PELA EXTRAÇÃO DE ARGILA

ABSTRACT: The activity of clay extraction implicates in the retreat of the natural vegetation and intense soil movement, generating in some cases considerable holes that contribute to the disturbance of the area, besides promoting with the retreat of the nutrients, high toxicity of metals in the soil. Due to the need of the recovery of the impacted ecosystems, this work has as objective the production and distribution of native arboreal seedlings inoculated with Arbuscular Mycorrhizal Fungi (AMF), rehabilitation of these areas. 9717 seedlings of arboreal and fruitful forest species were produced inoculated with mushrooms micorrízicos, being chosen in agreement with a meticulous study of the occurrence of the vegetation before existent in the area. Among them they are: açaí açaí (Euterpe oleracea), leucena (Leucaena spp), jataí (Hymenaea stilhocarga Hayne), thrush (Mimosa caesalpiniaefolia), acerola (Malpighia glabra L.), piqui (Caryocar brasiliense Cambess), sumaúma (Ceiba pentandra (L.) Gaertn.), ingá (Inga spp.) and purple ipê (Tabebuia impetiginosa). After having sowed in plastic sacks and tubetes with a mixture of ravine soil, vermiculita and bovine manure, the seedlings were inoculated with coming FMAs of the cultivation trap with Brachiaria brizantha the vegetation home. The germination tax varied in agreement with the species, and 210 days after the germination were taken to field 1621 seedlings between December 23, 2009 and January 19, 2011. The survival tax in the field, in the different areas, varied in agreement with the species and chemical and physical quality of the soils, and in all of the areas the survival tax was superior to the 90%.   KEY-WORDS: clay exploration, recovery, mycorrhizae.RESUMO: A atividade de extração de argila implica na retirada da vegetação natural e intensa movimentação de solo promovendo com a retirada dos nutrientes, alta toxidez de metais no solo. Diante da necessidade da recuperação dos ecossistemas impactados, este trabalho teve como objetivo produzir mudas arbóreas nativas inoculadas com fungos micorrízicos arbusculares (FMAs), para reabilitar essas áreas. Foram produzidas 9717 mudas de espécies florestais arbóreas e frutíferas inoculadas com fungos micorrízicos, sendo escolhidas de acordo com um estudo minucioso da ocorrência da vegetação antes existente na área. Dentre elas estão: açaí (Euterpe oleracea), leucena (Leucaena spp), jataí (Hymenaea stilhocarga Hayne), sabiá (Mimosa caesalpiniaefolia), acerola (Malpighia glabra L.), piqui (Caryocar brasiliense Cambess), sumaúma (Ceiba pentandra (L.) Gaertn.), ingá (Inga spp.) e ipê roxo (Tabebuia impetiginosa). Após semeadas em sacos plásticos e tubetes com uma mistura de solo de barranco, vermiculita e esterco bovino, as mudas foram inoculadas com os FMAs provenientes do cultivo armadilha com Brachiaria brizantha da casa de vegetação. A taxa de germinação variou de acordo com as espécies, e 210 dias após a germinação foram levadas a campo 1621 mudas entre os dias 23 de dezembro de 2009 e 19 de janeiro de 2010. A taxa de sobrevivência no campo, nas diferentes áreas, variou de acordo com a espécie e qualidade química e física dos solos, sendo que em todas as áreas a taxa de sobrevivência foi superior à 90%. PALAVRAS-CHAVE: exploração de argila, recuperação, micorrizas

Importance of IL-10 Modulation by Probiotic Microorganisms in Gastrointestinal Inflammatory Diseases

Lactic acid bacteria (LAB) represent a heterogeneous group of microorganisms that are naturally present in many foods and possess a wide range of therapeutic properties. The aim of this paper is to present an overview of the current expanding knowledge of one of the mechanisms by which LAB and other probiotic microorganisms participate in the prevention and treatment of gastrointestinal inflammatory disease through their immune-modulating properties. A special emphasis will be placed on the critical role of the anti-inflammatory cytokine IL-10, and a brief overview of the uses of genetically engineered LAB that produce this important immune response mediator will also be discussed. Thus, this paper will demonstrate the critical role that IL-10 plays in gastrointestinal inflammatory diseases and how probiotics could be used in their treatment

In silico approaches for drug repurposing in oncology: a scoping review

Introduction: Cancer refers to a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body. Due to its complexity, it has been hard to find an ideal medicine to treat all cancer types, although there is an urgent need for it. However, the cost of developing a new drug is high and time-consuming. In this sense, drug repurposing (DR) can hasten drug discovery by giving existing drugs new disease indications. Many computational methods have been applied to achieve DR, but just a few have succeeded. Therefore, this review aims to show in silico DR approaches and the gap between these strategies and their ultimate application in oncology.Methods: The scoping review was conducted according to the Arksey and O’Malley framework and the Joanna Briggs Institute recommendations. Relevant studies were identified through electronic searching of PubMed/MEDLINE, Embase, Scopus, and Web of Science databases, as well as the grey literature. We included peer-reviewed research articles involving in silico strategies applied to drug repurposing in oncology, published between 1 January 2003, and 31 December 2021.Results: We identified 238 studies for inclusion in the review. Most studies revealed that the United States, India, China, South Korea, and Italy are top publishers. Regarding cancer types, breast cancer, lymphomas and leukemias, lung, colorectal, and prostate cancer are the top investigated. Additionally, most studies solely used computational methods, and just a few assessed more complex scientific models. Lastly, molecular modeling, which includes molecular docking and molecular dynamics simulations, was the most frequently used method, followed by signature-, Machine Learning-, and network-based strategies.Discussion: DR is a trending opportunity but still demands extensive testing to ensure its safety and efficacy for the new indications. Finally, implementing DR can be challenging due to various factors, including lack of quality data, patient populations, cost, intellectual property issues, market considerations, and regulatory requirements. Despite all the hurdles, DR remains an exciting strategy for identifying new treatments for numerous diseases, including cancer types, and giving patients faster access to new medications

QUEBRA DE DORMÊNCIA DO FAVÃO PARA O USO NA RECUPERAÇÃO DE ÁREAS DEGRADADAS EM MARABÁ-PA

ABSTRACT: The recovery of degraded areas becomes an alternative for the environment and society. Marabá-PA in areas where activities clay extraction is conducted is degradation. O bean (Parkia multijuga Beth) is a legume and is a common occurrence in the Amazon region. The aim of this study was to determine the best method of breaking dormancy for Fava, noting the rate germination. The experiment in the greenhouse was a factorial in completely randomized design (CRD), containing a plant species, a type of substrate, Three methods of breaking dormancy which consisted of a control (without breaking dormancy) (TR1), mechanical scarification (TR2) and Soaking in H2SO4 for 16 minutes (TR3), where it used to 40 repetitions, totaling 120 pots (1x1x3x40). For the germination data was used three simple rule using the value of the quantity of seeds germinated with the amount of seeds sown. The data were analyzed and subjected to the tests mean and variance of Tukey at 5% probability, using methods described in the software SISVAR. The method to overcome dormancy of bean was the most efficient chiseling.   KEY-WORDS: germination, Parkia multijuga, rehabilitation.RESUMO: A recuperação de áreas degradadas torna-se uma alternativa para o meio ambiente e social. Em Marabá-PA áreas em que são realizadas atividades de extração de argila encontram-se degradadas.O favão (Parkia multijuga Beth) é uma leguminosa e é comum sua ocorrência na região Amazônica. O objetivo deste trabalho foi verificar o melhor método de quebra de dormência para o favão, observando a taxa de germinação. O delineamento experimental em casa de vegetação foi um fatorial no delineamento inteiramente casualizado (DIC), contendo uma espécie vegetal, um tipo de substrato, três métodos de quebra de dormência que consistiu em testemunha (sem quebra de dormência) (TR1), escarificação mecânica (TR2) e imersão das sementes em H2SO4, por 16 minutos (TR3), onde usou-se 40 repetições , totalizando 120 vasos (1x1x3x40). Para obter os dados da germinação foi usado regra de três simples usando o valor da quantidade de sementes germinada com a quantidade de sementes semeadas. Os dados foram analisadas e submetidas a testes de média e de variância de Tukey a 5% de probabilidade, segundo metodologia descrita no software SISVAR.. O método de superação da dormência do favão mais eficiente foi a escarificação mecânica. PALAVRAS-CHAVES: germinação, Parkia multijuga, reabilitação

AVALIAÇÃO E DISTRIBUIÇÃO DE MUDAS DE ESPÉCIES ARBÓREAS INOCULADAS COM FUNGOS MICORRÍZICOS PARA ATUAR NA REABILITAÇÃO DE ÁREAS IMPACTADAS PELA EXTRAÇÃO DE ARGILA EM MARABÁ-PA

RESUMEN: La exploración de la arcilla en la ciudad de Marabá ha provocado una serie de impactos negativos sobre el medio ambiente físico. La actividad de extracción de arcilla implica la eliminación de la vegetación natural y el intenso movimiento de suelo, la creación de agujeros considerables en algunos casos contribuyen a la alteración de la zona, y promover la retirada de nutrientes, toxicidad de los metales de alta en el suelo. Dada la necesidad de la restauración de los ecosistemas afectados, su objetivo es la producción de plántulas de árboles nativos inoculadas con hongos micorrizógenos arbusculares (HMA), en sustitución de la vegetación existente antes, servir como cerca viva para contener la erosión hídrica y eólica del suelo y proporcionar un entorno propicio para el desarrollo de las comunidades microbianas del suelo, determinar el porcentaje de germinación de cada especie. El inóculo de HMA se produce a través de la cultura de la trampa con Brachiaria brizantha en un invernadero. Las plántulas de acacia y el tordo se produjeron con una superficie del sustrato de relaves y 90 días fueron inoculadas con la AMF a los 120 días y trasladado al campo. La tasa de germinación en invernadero total varió según la especie y que el tordo tenía una tasa de germinación de 9,3% y el 32,5% de Acacia. A los 60 días después de la germinación de las plántulas de acacia había un mejor desarrollo en altura, número de hojas, número de pecíolo, el número de cotiledones y el número de hojas, en comparación con las plántulas en el campo de sabiá y estan teniendo un desarrollo uniforme y satisfactorio.   PALABRAS CLAVE: Exploración de la arcilla, restauración del paisaje, micorrizas.RESUMO: A exploração de argila na cidade de Marabá tem causado uma série de impactos negativos ao meio físico. A atividade de extração de argila implica na retirada da vegetação natural e intensa movimentação de solo, gerando em alguns casos consideráveis buracos que contribuem para o distúrbio da área, além de promover com a retirada dos nutrientes, alta toxidez de metais no solo. Diante da necessidade da recuperação dos ecossistemas impactados, este tem como objetivo a produção de mudas arbóreas nativas inoculadas com fungos micorrízicos arbusculares (FMAs), para repor a vegetação antes existente, servir de cerca viva para conter a erosão hídrica e eólica do solo e propiciar um ambiente favorável ao desenvolvimento da microbiota do solo, avaliando a taxa de germinação de cada espécie. O inóculo de FMAs está sendo produzido através do cultivo armadilha com Brachiaria brizantha em casa de vegetação. As mudas de sabiá e acácia foram produzidas com substrato da área de rejeito e aos 90 dias foram inoculados com os FMAs e aos 120 dias levadas à campo. A taxa de germinação em casa de vegetação total variou de acordo com a espécie, sendo que o sabiá teve uma taxa de germinação de 9,3% e de Acácia 32,5%. Aos 60 dias após a germinação as mudas de acácia tiveram um melhor desenvolvimento em altura, número de folhas, número de pecíolos, número de cotilédones e número de folíolos, quando comparadas as mudas de sabiá e no campo estão tendo desenvolvimento uniforme e satisfatório.   PALAVRAS-CHAVE: Exploração de argila, recuperação paisagística, micorrizas

Qualidade de vida: conceito e variáveis relacionadas

Devido à falta de um conceito amplamente aceito a qualidade de vida é tratada por diferentes óticas conforme a área e a situação de interesse, sendo, em muitos casos, considerada sinônimo de saúde. Assim, este artigo tem por objetivo realizar uma apresentação de algumas abordagens conceituais e discutir algumas variáveis relacionadas à qualidade de vida como saúde, estilo de vida, bem-estar, felicidade, liberdade, autonomia, possibilidades de crescimento e percepção. As leituras realizadas apontam para a necessidade do tema ser tratado de forma ampla e multidisciplinar e da investigação de estratégias claras para a promoção da qualidade de vida dos indivíduos