Clinics
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FOXO3a dysregulation is frequently implicated in tumorigenesis, and its inhibition can occur by several molecular mechanisms. Among these, post-transcriptional suppression by miRNAs has been associated with various cancers initiation. Here, we assessed the expression profiles of the most relevant miRNAs for breast tumorigenesis, using Luminal A (LA) and Triple-Negative (TN) breast cancer from Brazilian patients, by the quantitative real time-PCR method. ⋯ Reduced protein detection was observed in all of the tumors compared to normal tissues. The most prominent miRNA expression and FOXO3a protein suppression were observed in TN samples (p < 0.001), indicating the relevant role of these molecules in this tumor biology and clinical behavior. Our results corroborate the literature regarding to the relevance of FOXO3a in the breast cancer, and they open new perspectives for alternative target therapy options for Brazilian patients expressing both FOXO3a and its regulatory miRNAs.
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To describe the speech pattern of patients with hereditary Spastic Paraplegia type 4 (SPG4) and correlated it with their clinical data. ⋯ Dysarthria in SPG4 is frequent and mild, and it did not evolve in conjunction with more advanced motor diseases. This data suggest that diagnosed patients should be screened and referred for speech therapy evaluation and those pathophysiological mechanisms of speech involvement may differ from the length-dependent degeneration of the corticospinal tract.
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Review
Programmed cell death-1 and its ligands: Current knowledge and possibilities in immunotherapy.
Programmed Cell Death-1 (PCD-1) is a key immune checkpoint receptor, which mainly expresses on activated T, B, Dendritic (DC), Natural Killer (NK), and Treg cells. On the surface of activated T-cells, PCD-1 expression is upregulated after the recognition of peripherals antigens by T cells; subsequently, the elevated binding of PD-1 to Programmed Death Ligand-1 (PD-L1) and Programmed Death Ligand-2 (PD-L2) becomes a key step for downstream inhibitory signaling. ⋯ The complex interplay between these factors plays a major role in the diffusion and clinical application of PD-L1 IHC assays as predictive biomarkers of response to PD-1/PD-L1 inhibitors. Checkpoint blockades are registered for the treatment of various cancers, including gynecological malignancies.
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Although miR-653-5p has been validated to participate in the progression of multiple types of cancer, the functional role of exosomal miR-653-5p derived from Mesenchymal Stem Cells (MSCs) in Laryngeal Papilloma (LP) has still remained elusive. Hence, this study aimed to investigate the role of MSCs-derived exosomal miR-653-5p in LP. ⋯ chictr-ior-17011021.
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COVID-19 can converge with the pro-inflammatory immunoregulatory mechanisms of chronic lung diseases. Given the disorders inherent to lung transplantation and the inexistence of other definitive therapeutic alternatives, Adipose tissue-derived Stem Cells (ASCs) presented themselves as a therapeutic hope. The purpose of this review is to assess the basis for the potential use of ASCs in lung diseases unresponsive to conventional therapy, relating to their possible use in COVID-19 ARDS. 35 studies comprised this review, 14 being narrative reviews, 19 preclinical trials and two proofs of concept. ⋯ Its detailed reading indicated the absence of serious adverse effects and toxicity to the administration of ASCs and suggested possible effectiveness in reducing lung damage, in addition to promoting the recovery of leukocytes and lymphocytes with its immunomodulatory and anti-apoptotic effects. The revised clinical data suggests optimism in the applicability of ASCs in other immunoinflammatory diseases and in severe COVID-19 ARDS. However, further studies are needed to develop a consensus on the methods of collection of ASCs, the ideal dosage schedule, the most effective time and route of administration, as well as on the definition of indications for the administration of ASCs in cases of COVID-19 for conducting clinical trials in near future.