O Uso terapêutico de mediadores anti-inflamatórios da via do ácido araquidônico

Arachidonic acid (AA) a precursor in the formation of eicosanoids which are lipid mediators with a number of functions in human physiology and pathology. The most of the eicosanoids act as proinflammatory mediators and contribute to the development and proliferation of tumors. In this thesis we evaluated two mediators: 15-deoxy-Δ12,14-PGJ2 (15d- PGJ2) and epoxieicosatrienoic acids (EETs) both act with an opposite activity of most eicosanoids, with an anti-inflammatory and and anti-tumoral action these two distinct mediators from AA pathway were used in this thesis in two different projects. First: 15d- PGJ2, was described that to have an antiproliferative activity and to induce apoptosis in several types of tumor cells however, the effect of 15d- PGJ2 in thyroid cancer cells was unknown in this sense, we tested in vitro cultured thyroid tumor cells, here in TPC1 cells, and treated with different concentrations of 15d- PGJ2 (0 to 20 uM) the treated cells showed a decrease in proliferation and an increase in apoptosis and a decrease in IL-6 release and relative expression. These key results together demonstrate that 15d- PGJ2 can be used as a new therapy for thyroid cancer. Second: The EETs are converted to their diols by soluble epoxy hydrolase (sEH) to maintain the stability of EETs and their anti-inflammatory activity, an inhibitor (TPPU) against was used to sEH in a periodontitis model induced with Aggregatibacter actinomycetemcomitans. The oral treatment in mice with TPPU and sEH Knockout animals showed bone loss reduction accompanied by a decrease in the osteoclastogenic molecules, like RANK, RANKL and OPG, demonstrating that pharmacological inhibition of sEH may have therapeutic value in periodontitis and inflammatory diseases that involve bone resorption.Tese (Doutorado)O ácido araquidônico (AA) é precursor na formação dos eicosanoides, que são mediadores lipídicos com uma série de funções na fisiologia e patologia humana. A maioria dos eicosanoides atuam como mediadores pró-inflamatórios e contribuem para o desenvolvimento e proliferação de tumores. Nesta tese foram avaliados dois mediadores: a 15-deoxi-Δ12,14-PGJ2 (15d- PGJ2) e os ácidos Epoxieicosatrienoicos (EETs), ambos apresentam uma atividade oposta a da maioria dos eicosanoides, ou seja, com uma ação anti-inflamatória e antitumoral. Esses dois mediadores distintos da via do AA foram utilizados nesta tese em dois projetos distintos. Primeiro: A 15d- PGJ2 possui uma atividade antiproliferativa e induziu apoptose para diversos tipos de células tumorais, entretanto, o efeito da15d- PGJ2 em células de cancer da tireoide ainda estava desconhecido. Neste sentido, foram cultivadas in vitro células tumorais da tireoide, da linhagem TPC1, e tratadas com diferentes concentrações de 15d- PGJ2 (0 ate 20 μM), as células tratadas demonstraram uma diminuição na proliferação, e aumento na apoptose, e uma diminuição na liberação e expressão relativa de IL-6. Estes resultados em conjunto sugerem que a 15d- PGJ2 pode ser utilizada como uma nova terapia para o cancer da tireoide. Segundo: Os EETs são metabolizados em seus diois pela epóxi hidrolase solúvel (sEH), para manter a estabilidade dos EETs e a sua atividade antiiflamatoria, foi utilizado um inibidor (TPPU) para sEH em um modelo de periodontite induzida por Aggregatibacter actinomycetemcomitans. O tratamento oral com TPPU, assim como o uso de animais sEH Knockout, levou a uma redução na perda óssea acompanhada da diminuição de moléculas osteoclastogenicas como RANK, RANKL e OPG, demonstrando que a inibição farmacológica da sEH pode ter um valor terapêutico na periodontite e doenças inflamatórias que envolvem a reabsorção óssea

15-deoxy-delta(12,14)-prostaglandin J(2) Induces Apoptosis And Upregulates Socs3 In Human Thyroid Cancer Cells

The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a natural ligand of peroxisome proliferator-activated receptor gamma (PPAR-gamma) and a potential mediator of apoptosis in Cancer Cells. In the present study, we evaluated the effect of 15d-PGJ(2) in human thyroid papillary carcinoma cells (TPC-1) using different doses of 15d-PGJ(2) (0.6 to 20 mu M) to determine IC50 (9.3 mu M) via the MTT assay. The supernatant culture medium of the TPC-1 cells that was treated either with 15d-PGJ(2) or with vehicle (control) for 24 hours was assessed for IL-6 secretion via CBA assay. RT-qPCR was used to evaluate mRNA expression of IL-6, SOCS1, SOCS3, and STAT3. TPC-1 cells treated with 15d-PGJ(2) decreased the secretion and expression of IL-6 and STAT3, while it increased SOCS1 and SOCS3. Overall, we demonstrated that 15d-PGJ(2) downregulated IL-6 signaling pathway and led TPC-1 cells into apoptosis. In conclusion, 15d-PGJ(2) shows the potential to become a new therapeutic approach for thyroid tumors

Brazils Highway BR-319: The road to the collapse of the Amazon and the violation of indigenous rights

One of the greatest threats to the Brazilian Amazon is the reconstruction and paving of the formerly abandoned Highway BR-319, which would link one of the most conserved blocks in the Amazon forest to the “arc of deforestation” on the southern edge of the region where most forest has already been destroyed. BR-319 and its planned side roads would allow the actors and processes from the arc of deforestation to move into vast areas of unprotected rainforest. In the specific case of this highway, a judicial decision that is not subject to further appeal established that environmental studies for the first section of the highway to be reconstructed (“Lot C”) must be carried out before paving. The federal highway department and the “Civil House” of President Bolsonaro’s presidential office ignored this decision and issued a call for bids for the construction work. Due to the current lack of governance in the BR-319 area and the history of deforestation whenever Amazonian highways are built, the decision on whether to suspend the contract for the “Lot C” is critical for the maintenance of both the ecosystem services of the Amazon forest and the way of life of indigenous and riverside people. This decision is expected to be made shortly by a single person

ESTUDO BIOMÉTRICO DE RATOS ALIMENTADOS COM DOIS TIPOS DE DIETA

A dieta hipercalórica é tida como fator de risco para o desenvolvimento de doenças cardiovasculares, sendo preocupante para a saúde pública mundial. O objetivo do presente estudo foi comparar a biometria de ratos alimentados por dois tipos de dieta. Para tanto, foram utilizados 24 ratos Wistar machos com 90 dias com oferta de ração e água à vontade; divididos em G1 recebendo dieta normocalórica e G2, dieta hipercalórica. A ingesta alimentar foi mensurada diariamente. Após 18 semanas foram eutanasiados, com prévia mensuração de massa corpórea, comprimento naso-anal e cáculo do índice de Lee. Os dados foram tratados por estatística descritiva, com uso do teste de normalidade de Kolmogorov-Smirnov seguido por ANOVA - One Way e pós-teste de Tukey; com significância de 5%. O grupo G2 apresentou maior ganho de peso e conseqüentemente índice de Lee superior ao G1, porém houve diminuição do consumo alimentar de G2 em comparação a G1

Seroprevalence of Chikungunya virus and living conditions in Feira de Santana, Bahia-Brazil.

BACKGROUND: Chikungunya is an arbovirus, transmitted by Aedes mosquitoes, which emerged in the Americas in 2013 and spread rapidly to almost every country on this continent. In Brazil, where the first cases were detected in 2014, it currently has reached all regions of this country and more than 900,000 cases were reported. The clinical spectrum of chikungunya ranges from an acute self-limiting form to disabling chronic forms. The purpose of this study was to estimate the seroprevalence of chikungunya infection in a large Brazilian city and investigate the association between viral circulation and living condition. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a population-based ecological study in selected Sentinel Areas (SA) through household interviews and a serologic survey in 2016/2017. The sample was of 1,981 individuals randomly selected. The CHIKV seroprevalence was 22.1% (17.1 IgG, 2.3 IgM, and 1.4 IgG and IgM) and varied between SA from 2.0% to 70.5%. The seroprevalence was significantly lower in SA with high living conditions compared to SA with low living condition. There was a positive association between CHIKV seroprevalence and population density (r = 0.2389; p = 0.02033). CONCLUSIONS/SIGNIFICANCE: The seroprevalence in this city was 2.6 times lower than the 57% observed in a study conducted in the epicentre of the CHIKV epidemic of this same urban centre. So, the herd immunity in this general population, after four years of circulation of this agent is relatively low. It indicates that CHIKV transmission may persist in that city, either in endemic form or in the form of a new epidemic, because the vector infestation is persistent. Besides, the significantly lower seroprevalences in SA of higher Living Condition suggest that beyond the surveillance of the disease, vector control and specific actions of basic sanitation, the reduction of the incidence of this infection also depends on the improvement of the general living conditions of the population

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio