Danielle Maria Nascimento Moura

Background: Chemical modifications of mRNAs constitute an alternative mechanism for gene expression regulation, which involves proteins responsible for adding, recognizing and removing these modifications. While orthologs of enzymes involved in adding m1A (TRMT6/TRMT61A) and m5C (NSUN2) modifications are present in trypanosomatid species, a clear understanding of their biological role in these parasites is necessary. Methods: To shed light on this, we genetically manipulated the TRMT61A and NSUN2 protein-encoding genes in the Leishmania mexicana species using the CRISPR-Cas9 editing technique and analyzed the impact on cell growth and differentiation as well as the global gene expression profile. Results: Deletion of the genes investigated here caused changes in the normal pattern of L. mexicana differentiation, and functional analyses of differentially expressed genes in the mutants unveiled significant biological effects. For the TRMT61A gene, transcripts related to nucleotide metabolism, translation, protein folding and refolding were affected. For the NSUN2 genes, enrichment analysis indicated impacts on biological processes mostly related to nucleotide metabolism and DNA binding. Conclusions: Our findings provide insights into the role of these methyltransferases orthologs in the regulation of trypanosomatid transcriptome, contributing to our understanding of gene expression control in this parasite. Graphical

Liver diseases especially hepatitis, alcoholic liver disease (ALD), and cancer are among the main causes of morbidity-mortality worldwide. Here, we analyzed data on hospital admissions, prevalence and mortality rates due to ALD, liver cancer, viral hepatitis and schistosomiasis in northeastern Brazil between 2000-2020, and investigate possible impacts caused by the COVID-19 pandemic in these data. In this period, Pernambuco (PE) and Bahia (BA) stood out for the growth in admissions for ALD: 707.2% and 177.3%, respectively; Paraiba (PB), Ceará (CE), and Alagoas (AL) showed the highest prevalence: 9.8%, 7.9%, 6.8%, respectively; and Maranhão (MA) showed the lowest: 2.1%. The highest mortality rates were RN (22.8%), SE (22.1%), and the lowest, PI (9.5%). For Neoplasms, we highlight PE, BA, and CE with increases of 659.4%, 934.6%, and 1,069.6% in admissions, respectively. Regarding mortality, the highest averages were observed for BA (31.1%), and CE (17.9%). However, in this period, admissions due to hepatitis were reduced about 70% in the country. The highest prevalence means in the period were MA (7.37%) and PE (6.38%). PE had the highest mean mortality (9.1%), followed by BA (7.1%). Hospitalizations for schistosomiasis decreased between 2000-2020, with emphasis to AL (98.4%), BA (92.3%), and PE (93.4%). The same was observed for prevalence and mortality. Analyzing admissions data from 2020 compared to the average from 2015 to 2019, a significant decrease in hospitalizations due to hepatitis, ALD, and schistosomiasis was observed. However, admissions for liver cancer increased. These data show the importance of epidemiological screening of liver diseases in Brazilian regions and highlight the need for a thorough mapping of the real impact of the COVID-19 pandemic on health data recording systems in the country.

It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect residents of impoverished regions in tropical and subtropical countries. The main species responsible for causing disease in humans are Schistosoma Mansoni, S. japonicum, and S. haematobium, each with different geographic distributions. Praziquantel is the drug predominantly used to treat this disease, which offers low effectiveness against immature and juvenile parasite forms. In addition, reports of drug resistance prompt the development of novel therapeutic approaches. Natural products represent an important source of new compounds, especially those obtained from plant sources. This review compiles data from several in vitro and in vivo studies evaluating various compounds and essential oils derived from plants with cercaricidal and molluscicidal activities against both juvenile and adult forms of the parasite. Finally, this review provides an important discussion on recent advances in molecular and computational tools deemed fundamental for more rapid and effective screening of new compounds, allowing for the optimization of time and resources.