Efficacy and Safety of Chagas Disease Drug Therapy and Treatment Perspectives

Chagas disease, also known as American trypanosomiasis, is a neglected disease caused by the protozoan parasite Trypanosoma cruzi. The disease affects about 6–7 million people worldwide, mostly in Latin America. Although Chagas disease was discovered more than 100 years ago, and the first treatments over 40, only 2 drugs were used to treat this pathology, it is still considered one of the neglected diseases. In this chapter, the subjects related to conventional etiological therapies, benznidazole and nifurtimox, such as the drug, the mechanism of action, the therapy schedule for treatment, efficacy and safety and their adverse effects will be discussed. Additionally, it will address alternative therapies of comorbidities related to the progression of Chagas’ disease in patients with chronic disease, such as heart disease and dysfunction of the digestive system. Finally, novel pharmacological strategies and their related compounds will be reviewed accounting for their progression in pharmacological studies and their success rate

Hypoxia enhances ILC3 responses through HIF-1α-dependent mechanism

Group 3 innate lymphoid cells (ILC3) have a prominent role in the maintenance of intestine mucosa homeostasis. The hypoxia-inducible factor (HIF) is an important modulator of immune cell activation and a key mechanism for cellular adaptation to oxygen deprivation. However, its role on ILC3 is not well known. In this study, we investigated how a hypoxic environment modulates ILC3 response and the subsequent participation of HIF-1 signaling in this process. We found increased proliferation and activation of intestinal ILC3 at low oxygen levels, a response that was phenocopied when HIF-1α was chemically stabilized and was reversed when HIF-1 was blocked. The increased activation of ILC3 relied on a HIF-1α-dependent transcriptional program, but not on mTOR-signaling or a switch to glycolysis. HIF-1α deficiency in RORyt compartment resulted in impaired IL-17 and IL-22 production by ILC3 in vivo, which reflected in a lower expression of their target genes in the intestinal epithelium and an increased susceptibility to Clostridiodes difficile infection. Taken together, our results show that HIF-1α activation in intestinal ILC3 is relevant for their functions in steady state and infectious conditions

Yield and validation of the scanner for use in the estimation of number of sunflower grains

The commercial exploitation of sunflower is based on the extraction of oil from the achenes and the bran produced, being one of the most important oil supplying species in the world. The objective of the work was to verify the yield of grains from commercial crops in the sunflower and to validate the method of using the scanner for the seed count. The data were collected in two commercial crops, located in the municipalities of Diamantino-MT and Campo Novo dos Parecis-MT. The variables were evaluated between January and July 2014: grain yield, grain yield components and plant height. The seed count was done manually and through an HP Photosmart C4480 All-in-One Scanner scanner, and the images were processed to estimate the number of seeds per chapter in the Quant.v program. 1.0.2. Grain yield data were correlated with grain yield components. The mass of achenes per chapter showed a significant correlation with grain yield. In order to calibrate the digitized images, 1190 and 1107 seeds in the agrobel and aguara varieties, respectively, are adequate, and the seed counting method with the digitizer is accurate and can replace the manual method, in addition, it allows to work with larger samples of achenes per chapter with less time spent

A distinct human cell type expressing MHCII and RORγt with dual characteristics of dendritic cells and type 3 innate lymphoid cells

Recent studies have characterized various mouse antigen- presenting cells (APCs) express -ing the lymphoid- lineage transcription factor ROR gamma t (Retinoid- related orphan receptor gamma t), which exhibit distinct phenotypic features and are implicated in the induc-tion of peripheral regulatory T cells (Tregs) and immune tolerance to microbiota and self- antigens. These APCs encompass Janus cells and Thetis cell subsets, some of which express the AutoImmune REgulator (AIRE). ROR gamma t+ MHCII+ type 3 innate lymphoid cells (ILC3) have also been implicated in the instruction of microbiota- specific Tregs. While ROR gamma t+ APCs have been actively investigated in mice, the identity and function of these cell subsets in humans remain elusive. Herein, we identify a rare subset of ROR gamma t+ cells with dendritic cell (DC) features through integrated single -cell RNA sequencing and single -cell ATAC sequencing. These cells, which we term ROR gamma t+ DC -like cells (R- DC- like), exhibit DC morphology, express the MHC class II machinery, and are distinct from all previously reported DC and ILC3 subsets, but share transcriptional and epigenetic similarities with DC2 and ILC3. We have developed procedures to isolate and expand them in vitro, enabling their functional characterization. R -DC -like cells proliferate in vitro, continue to express ROR gamma t, and differentiate into CD1c+ DC2-like cells. They stimulate the proliferation of allogeneic T cells. The identification of human R -DC -like cells with proliferative potential and plasticity toward CD1c+ DC2-like cells will prompt further investigation into their impact on immune homeostasis, inflam-mation, and autoimmunity