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      Copaifera spp. oleoresins impair Toxoplasma gondii infection in both human trophoblastic cells and human placental explants

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          Abstract

          The combination of pyrimethamine and sulfadiazine is the standard care in cases of congenital toxoplasmosis. However, therapy with these drugs is associated with severe and sometimes life-threatening side effects. The investigation of phytotherapeutic alternatives to treat parasitic diseases without acute toxicity is essential for the advancement of current therapeutic practices. The present study investigates the antiparasitic effects of oleoresins from different species of Copaifera genus against T. gondii. Oleoresins from C. reticulata, C. duckei, C. paupera, and C. pubiflora were used to treat human trophoblastic cells (BeWo cells) and human villous explants infected with T. gondii. Our results demonstrated that oleoresins were able to reduce T. gondii intracellular proliferation, adhesion, and invasion. We observed an irreversible concentration-dependent antiparasitic action in infected BeWo cells, as well as parasite cell cycle arrest in the S/M phase. The oleoresins altered the host cell environment by modulation of ROS, IL-6, and MIF production in BeWo cells. Also, Copaifera oleoresins reduced parasite replication and TNF-α release in villous explants. Anti- T. gondii effects triggered by the oleoresins are associated with immunomodulation of the host cells, as well as, direct action on parasites.

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          Most cited references 79

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          Toxoplasmosis snapshots: global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis.

          Toxoplasma gondii's importance for humans refers mainly to primary infection during pregnancy, resulting in abortion/stillbirth or congenital toxoplasmosis. The authors sought to evaluate the current global status of T. gondii seroprevalence and its correlations with risk factors, environmental and socioeconomic parameters. Literature published during the last decade on toxoplasmosis seroprevalence, in women who were pregnant or of childbearing age, was retrieved. A total of 99 studies were eligible; a further 36 studies offered seroprevalence data from regions/countries for which no data on pregnancy/childbearing age were available. Foci of high prevalence exist in Latin America, parts of Eastern/Central Europe, the Middle East, parts of south-east Asia and Africa. Regional seroprevalence variations relate to individual subpopulations' religious and socioeconomic practices. A trend towards lower seroprevalence is observed in many European countries and the United States of America (USA). There is no obvious climate-related gradient, excluding North and Latin America. Immigration has affected local prevalence in certain countries. We further sought to recognise specific risk factors related to seropositivity; however, such risk factors are not reported systematically. Population awareness may affect recognition of said risks. Global toxoplasmosis seroprevalence is continuingly evolving, subject to regional socioeconomic parameters and population habits. Awareness of these seroprevalence trends, particularly in the case of women of childbearing age, may allow proper public health policies to be enforced, targeting in particular seronegative women of childbearing age in high seroprevalence areas.
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            ROS, mitochondria and the regulation of autophagy.

            Accumulation of reactive oxygen species (ROS) is an oxidative stress to which cells respond by activating various defense mechanisms or, finally, by dying. At low levels, however, ROS act as signaling molecules in various intracellular processes. Autophagy, a process by which eukaryotic cells degrade and recycle macromolecules and organelles, has an important role in the cellular response to oxidative stress. Here, we review recent reports suggesting a regulatory role for ROS of mitochondrial origin as signaling molecules in autophagy, leading, under different circumstances, to either survival or cell death. We then discuss the relationship between mitochondria and autophagosomes and propose that mitochondria have an essential role in autophagosome biogenesis.
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              Management of Toxoplasma gondii infection during pregnancy.

              Acute infection with Toxoplasma gondii during pregnancy and its potentially tragic outcome for the fetus and newborn continue to occur in the United States, as well as worldwide, despite the fact that it can be prevented. The infection can be acquired through ingestion of infected, undercooked meat or contaminated food or water. Transmission to the fetus occurs almost solely in women who acquire their primary infection during gestation and can result in visual and hearing loss, mental and psychomotor retardation, seizures, hematological abnormalities, hepatosplenomegaly, or death. Systematic education and serological screening of pregnant women are the most reliable and currently available strategies for the prevention, diagnosis, and early treatment of the infection in the offspring; this is largely because toxoplasmosis in pregnant women most often goes unrecognized. Treatment of the infection in the fetus and infant during the first year of life has been demonstrated to significantly improve the clinical outcome.
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                Author and article information

                Contributors
                eloisa.ferro@ufu.br
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                16 September 2020
                16 September 2020
                2020
                : 10
                Affiliations
                [1 ]GRID grid.411284.a, ISNI 0000 0004 4647 6936, Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Science, , Federal University of Uberlândia, ; Campus Umuarama, Av. Para, 1720, Uberlândia, MG 38400239 Brazil
                [2 ]GRID grid.411284.a, ISNI 0000 0004 4647 6936, Department of Immunology, Biomedical Sciences Institute, , Federal University of Uberlândia, ; Uberlândia, Brazil
                [3 ]GRID grid.412276.4, ISNI 0000 0001 0235 4388, Nucleus of Research in Technological and Exact Sciences, , University of Franca, ; Franca, Brazil
                [4 ]GRID grid.11899.38, ISNI 0000 0004 1937 0722, School of Pharmaceutical Sciences of Ribeirao Preto, , University of São Paulo, ; Ribeirão Preto, Brazil
                [5 ]GRID grid.411284.a, ISNI 0000 0004 4647 6936, Department of Microbiology, Biomedical Sciences Institute, , Federal University of Uberlândia, ; Uberlândia, Brazil
                Article
                72230
                10.1038/s41598-020-72230-0
                7495442
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004901, Fundação de Amparo à Pesquisa do Estado de Minas Gerais;
                Funded by: FundRef http://dx.doi.org/10.13039/501100002322, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior;
                Funded by: FundRef http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Funded by: FundRef http://dx.doi.org/10.13039/501100001807, Fundação de Amparo à Pesquisa do Estado de São Paulo;
                Categories
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                © The Author(s) 2020

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                parasitic infection, pathogens, cell biology

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