ABSTRACT
Introduction: Breast cancer represents the most prevalent malignancy among women. Recent advancements in translational research have focused on the identification of novel biomarkers capable of providing valuable insights into patient outcomes. Furthermore, comprehensive investigations aimed at discovering novel miRNAs, unraveling their biological functions, and deciphering their target genes have significantly contributed to our understanding of the roles miRNAs play in tumorigenesis. Consequently, these investigations have facilitated the way for the development of miRNA-based approaches for breast cancer prognosis, diagnosis, and treatment. However, conducting a more extensive array of studies, particularly among diverse ethnic groups, is imperative to expand the scope of research and validate the significance of miRNAs. This study aimed to assess the expression patterns of circulating miRNAs in plasma as a prospective biomarker for breast cancer patients within a population primarily consisting of individuals from Black, Indigenous, and People of Color (BIPOC) communities. Methods: We evaluated 49 patients with breast cancer compared to 44 healthy women. Results and discussion: All miRNAs analyzed in the plasma of patients with breast cancer were downregulated. ROC curve analysis of miR-21 (AUC = 0.798, 95% CI: 0.682-0.914, p <0.0001), miR-1 (AUC = 0.742, 95% CI: 0.576-0.909, p = 0.004), miR-16 (AUC = 0.721, 95% CI: 0.581-0.861, p = 0.002) and miR-195 (AUC = 0.672, 95% CI: 0.553-0.792, p = 0.004) showed better diagnostic accuracy in discrimination of breast cancer patients in comparison with healthy women. miR-210, miR-21 showed the highest specificities values (97.3%, 94.1%, respectively). Following, miR-10b and miR-195 showed the highest sensitivity values (89.3%, and 77.8%, respectively). The panel with a combination of four miRNAs (miR-195 + miR-210 + miR-21 + miR-16) had an AUC of 0.898 (0.765-0.970), a sensitivity of 71.4%, and a specificity of 100.0%. Collectively, our results highlight the miRNA combination in panels drastically improves the results and showed high accuracy for the diagnosis of breast cancer displaying good sensitivity and specificity.
ABSTRACT
Vascular reactivity experiments using isolated aortic rings have been widely used as a model for physiological and pharmacological studies since the early sixties. Here, we suggest several parameters that the researcher should pay attention to when investigating angiotensin II in their experimental models. Angiotensin II is one of the active peptides of the renin-angiotensin system and exerts its effect through the AT1 and AT2 receptors. Some studies seek to understand the effects of angiotensin II receptors at the vascular level by using vascular reactivity experiments. However, because of the large number of variations, there are only a handful of reactivity studies that seek to use this method. Thus, the objective of this study was to standardize experimental methods with angiotensin II, through vascular reactivity protocols. For this, variables such as basal tension, concentration interval, single concentration, curve concentration response, and multiple experiments using the same aortic ring were developed using the technique of vascular reactivity in an organ bath. This is the first study that has standardized the vascular reactivity protocol. In addition, we demonstrated the effects of TRV023-biased ligand of the AT1R at vascular sites.
