Smp38 MAP Kinase Regulation in Schistosoma mansoni: Roles in Survival, Oviposition, and Protection Against Oxidative Stress

Eukaryotic protein kinases (ePKs) are good medical targets for drug development in different biological systems. ePKs participate in many cellular processes, including the p38 MAPK regulation of homeostasis upon oxidative stress. We propose to assess the role of Smp38 MAPK signaling pathway in Schistosoma mansoni development and protection against oxidative stress, parasite survival, and also to elucidate which target genes have their expression regulated by Smp38 MAPK. After a significant reduction of up to 84% in the transcription level by Smp38 MAPK gene knockdown, no visible phenotypic changes were reported in schistosomula in culture. The development of adult worms was tested in vivo in mice infected with the Smp38 knocked-down schistosomula. It was observed that Smp38 MAPK has an essential role in the transformation and survival of the parasites as a low number of adult worms was recovered. Smp38 knockdown also resulted in decreased egg production, damaged adult worm tegument, and underdeveloped ovaries in females. Furthermore, only ~13% of the eggs produced developed into mature eggs. Our results suggest that inhibition of the Smp38 MAPK activity interfere in parasites protection against reactive oxygen species. Smp38 knockdown in adult worms resulted in 80% reduction in transcription levels on the 10th day, with consequent reduction of 94.4% in oviposition in vitro. In order to search for Smp38 MAPK pathway regulated genes, we used an RNASeq approach and identified 1,154 DEGs in Smp38 knockdown schistosomula. A substantial proportion of DEGs encode proteins with unknown function. The results indicate that Smp38 regulates essential signaling pathways for the establishment of parasite homeostasis, including genes related to antioxidant defense, structural composition of ribosomes, spliceosomes, cytoskeleton, as well as, purine and pyrimidine metabolism pathways. Our data show that the Smp38 MAPK signaling pathway is a critical route for parasite development and may present attractive therapeutic targets for the treatment and control of schistosomiasis

Identificação de variantes genéticas associadas com a perda gestacional

Miscarriage can be associated with a variety of genetic factors, hematological disorders, including changes in the anatomy of the uterus. Furthermore, there is a relationship between maternal age and reproductive health.Epidemiological studies reveal high rates of subfertility and spontaneous abortions linked to a range of these factors. Therefore, this study aims to investigate the genetic factors associated with pregnancy loss and promote the dissemination of results in a language accessible to the population, through a podcast channel with the aim of increasing awareness and facilitating access to appropriate health services. The study was performed through a narrative literature review. The development of the podcast channel was performed through recordings in an audiovisual environment with scripts developed based on the research results. Cytogenetic abnormalities representing around 50% of fetal deaths in the first trimester and 6% to 13% of stillbirths. Among the main alterations are trisomies of chromosomes 13, 18, 16, 22 and monosomy of chromosome X. Mutations in genes related to the cell cycle are also related to pregnancy loss due to the fact that they trigger serious congenital and developmental defects in embryos. Furthermore, hematological changes, such as thrombophilia and antiphospholipid syndrome, are related to pregnancy loss. This research unveiled the complexity of genetic interactions in the context of miscarriage, emphasizing the urgent need for interdisciplinary collaborations. The identification of specific genetic markers holds the potential to enhance screening and therapeutic strategies, underscoring the importance and recognition of the interconnection between genetic factors and physiological events during pregnancy.A perda gestacional pode ser relacionada a uma variedade de fatores genéticos, alterações hematológicas, além de alterações na anatomia uterina. Ainda a idade materna avançada possui relação entre a genética e saúde reprodutiva. Estudos epidemiológicos revelam elevadas taxas de subfertilidade e abortos espontâneos recorrentes, associados a uma gama desses fatores. Assim, o presente estudo teve como objetivo investigar os fatores genéticos associados à perda gestacional e promover a divulgação dos resultados com uma linguagem acessível à população, através de um canal de podcast, com a finalidade de ampliar a conscientização e facilitar o acesso a serviços de saúde adequados. O estudo foi realizado através de uma revisão narrativa da literatura. O desenvolvimento do canal de podcast foi realizado através de gravações em ambiente audiovisual com roteiros desenvolvidos a partir dos resultados da pesquisa. Anormalidades citogenéticas representam cerca de 50% das mortes fetais no primeiro trimestre e de 6% a 13% dos natimortos. Dentre as principais alterações se encontram as trissomias dos cromossomos 13, 18, 16, 22 e monossomia do cromossomo X. Alterações em genes relacionados ao ciclo celular também estão relacionadas à perda gestacional pelo fato de desencadear defeitos congênitos e de desenvolvimento graves em embriões. Ainda, as alterações hematológicas, como trombofilia e síndrome antifosfolipídeo estão relacionadas à perda gestacional. O presente estudo revelou a complexidade das interações genéticas no contexto da perda gestacional, destacando a necessidade premente de colaborações interdisciplinares. A identificação de marcadores genéticos específicos tem o potencial de aprimorar as estratégias de triagem e terapêuticas, enfatizando, portanto, a importância e reconhecimento da interconexão entre fatores genéticos e eventos fisiológicos da gravidez.&nbsp