RESUMO
Limb-girdle muscular dystrophies (LGMD) constitute a heterogeneous group of neuromuscular disorders in which there are alterations in proteins responsible for the preservation of muscle architecture and function, leading to proximal and progressive muscle weakness. There is, however, significant phenotypic and genotypic variation, as well as difficulty in establishing biomarkers that help to define pathogenic mechanisms and assess disease severity and progression. In this field, there is special attention to microRNAs, small non-coding RNA molecules related to the regulation of gene expression and, consequently, the production of proteins. Thus, this research aimed to verify the correlation between the expression of microRNAs and the severity, progression, and therapeutic response of LGMD animal models. A search was carried out in the PubMed, Embase, Scopus, ScienceDirect, Cochrane, and SciELO databases, with articles in English and without a time limit. The PRISMA 2020 checklist was used, and the protocol of this review was submitted to PROSPERO. The bibliographic survey of the 434 records found that 5 original articles met the inclusion criteria. The studies explored myomicroRNAs or miRNA panels with gene expression analysis. The analysis demonstrates that miR-1, 133a, and 206 are differentially expressed in serum and muscle. They change according to the degree of inflammation, fibrosis, muscle regeneration, and progression of the dystrophic process. MicroRNAs are up-regulated in dystrophic muscles, which are reversed after treatment in a dose-dependent manner. The present study inferred that miRs are essential in severity, progression, and therapeutic response in LGMD models and may be a useful biomarker in clinical research and prognosis. However, the practical application of these findings should be further explored.
RESUMO
Breast cancer is one of the most common malignancies among women around the world. The basal or triple-negative subtype (TNBC) is a heterogeneous group of tumors, characterized by its aggressive and metastatic nature, with low survival and worse prognosis. Research on genetic biomarkers, such as microRNAs (miRs) in TNBC, demonstrate their relevance in the prognosis of the disease. Therefore, the objective of this research was to verify the role of miRs in the prognosis of TNBC. A search was carried out in the PubMed (MEDLINE), Web of Science, and Scopus databases, with articles in the English language from 2010 to 2022. Only articles that analyzed the role of miRNAs in the prognosis of TNBC and that met the criteria of the MOOSE method were included. For the preparation and planning of this systematic review, a PRISMA checklist and the MOOSE method were used. The Newcastle-Ottawa Scale was used to analyze the quality of the included studies. The excluded criteria considered were: (1) studies that presented duplication in the databases; (2) reviews of the literature, clinical case reports, meta-analyses, conference abstracts, letters to the editor, theses, dissertations, and book chapters; (3) studies that stratified only women diagnosed with other subtypes of breast cancer subtypes; (4) experiments without a control or comparison group. After the bibliographic survey of the 2.274 articles found, 43 articles met the inclusion criteria, totaling 5421 patients with TNBC analyzed for this review. Six miRs (miR-155, miR-21, miR-27a/b/, miR-374a/b, miR-30a/c/e, and miR-301a) were included in the meta-analysis. A low expression of miR-155 was associated with reduced overall survival (OS) (HR: 0.68, 95% CI: 0.58-0.81). A high expression of miR-21 was a predictor of OS reduction (HR: 2.56; 95% CI: 1.49-4.40). In addition, high levels of miR-27a/b and miR-301a/b were associated with lower OS, while the decreased expression levels of miR-30 and miR-374a/b were associated with worse relapse-free survival (RFS) and shorter disease-free survival (DFS), respectively. The present study revealed that miRs play essential roles in the development of metastases, in addition to acting as suppressors of the disease, thus improving the prognosis of TNBC. However, the clinical application of these findings has not yet been investigated.
RESUMO
Biomarkers are valuable tools in clinical practice. In 2001, the National Institutes of Health (NIH) standardized the definition of a biomarker as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. A biomarker has clinical relevance when it presents precision, standardization and reproducibility, suitability to the patient, straightforward interpretation by clinicians, and high sensitivity and/or specificity by the parameter it proposes to identify. Thus, serum biomarkers should have advantages related to the simplicity of the procedures and to the fact that venous blood collection is commonplace in clinical practice. We described the potentiality of cfDNA as a general clinical biomarker and focused on endothelial dysfunction. Circulating cell-free DNA (cfDNA) refers to extracellular DNA present in body fluid that may be derived from both normal and diseased cells. An increasing number of studies demonstrate the potential use of cfDNA as a noninvasive biomarker to determine physiologic and pathologic conditions. However, although still scarce, increasing evidence has been reported regarding using cfDNA in cardiovascular diseases. Here, we have reviewed the history of cfDNA, its source, molecular features, and release mechanism. We also show recent studies that have investigated cfDNA as a possible marker of endothelial damage in clinical settings. In the cardiovascular system, the studies are quite new, and although interesting, stronger evidence is still needed. However, some drawbacks in cfDNA methodologies should be overcome before its recommendation as a biomarker in the clinical setting.
