The Renin-Angiotensin System (RAS) is classically recognized for regulating blood pressure and fluid balance. Recently, this role has extended to other areas including inflammation, obesity, diabetes, as well as breast cancer. RAS components are expressed in normal and cancerous breast tissues, and downregulation of RAS inhibits metastasis, proliferation, angiogenesis, and desmoplasia in the tumor microenvironment. Therefore, RAS inhibitors (Angiotensin receptor blockers, ARBs, or angiotensin converting enzyme inhibitors, ACE-I) may be beneficial as preventive adjuvant therapies to thwart breast cancer development and improve outcomes, respectively. Given the beneficial effects of RAS inhibitors in metabolic diseases, which often co-exist in breast cancer patients, combining RAS inhibitors with other breast cancer therapies may enhance the effectiveness of current treatments. This review scrutinizes above associations, to advance our understanding of the role of RAS in breast cancer and its potential for repurposing of RAS inhibitors to improve the therapeutic approach for breast cancer patients.Cryo-electron tomography provides the opportunity for unsupervised discovery of endogenous complexes in situ. This process usually requires particle picking, clustering and alignment of subtomograms to produce an average structure of the complex. When applied to heterogeneous samples, template-free clustering and alignment of subtomograms can potentially lead to the discovery of structures for unknown endogenous complexes. However, such methods require scoring functions to measure and accurately rank the quality of aligned subtomogram clusters, which can be compromised by contaminations from misclassified complexes and alignment errors. Here, we provide the first study to assess the effectiveness of more than 15 scoring functions for evaluating the quality of subtomogram clusters, which differ in the amount of structural misalignments and contaminations due to misclassified complexes. We assessed both experimental and simulated subtomograms as ground truth data sets. Our analysis showed that the robustness of scoring functions varies largely. Most scores were sensitive to the signal-to-noise ratio of subtomograms and often required Gaussian filtering as preprocessing for improved performance. Two scoring functions, Spectral SNR-based Fourier Shell Correlation and Pearson Correlation in the Fourier domain with missing wedge correction, showed a robust ranking of subtomogram clusters without any preprocessing and irrespective of SNR levels of subtomograms. Of these two scoring functions, Spectral SNR-based Fourier Shell Correlation was fastest to compute and is a better choice for handling large numbers of subtomograms.  https://www.selleckchem.com/products/lenalidomide-s1029.html  Our results provide a guidance for choosing an accurate scoring function for template-free approaches to detect complexes from heterogeneous samples.HOTAIR is a large, multi-exon spliced non-coding RNA proposed to function as a molecular scaffold and competes with chromatin to bind to histone modification enzymes. Previous sequence analysis and biochemical experiments identified potential conserved regions and characterized the full length HOTAIR secondary structure. Here, we examine the thermodynamic folding properties and structural propensity of the individual exonic regions of HOTAIR using an array of biophysical methods and NMR spectroscopy. We demonstrate that different exons of HOTAIR contain variable degrees of heterogeneity, and identify one exonic region, exon 4, that adopts a stable and compact fold under low magnesium concentrations. Close agreement of NMR spectroscopy and chemical probing unambiguously confirm conserved base pair interactions within the structural element, termed helix 10 of exon 4, located within domain I of human HOTAIR. This combined exon-biased and integrated biophysical approach introduces a new strategy to examine conformational heterogeneity in lncRNAs and emphasizes NMR as a key method to validate base pair interactions and corroborate large RNA secondary structures.Mitral regurgitation (MR) is a common condition causing significant morbidity and mortality in the Western world. Although surgical therapy has developed over 5 decades to provide solutions, only a minority of patients undergo surgery. The last decade has seen the emergence and application of multiple transcatheter techniques in attempts to address this undertreated population with the large clinical experience of MitraClip providing the most insight. Clear understanding of the pathophysiology of different MR types as well as the role of particularly secondary MR on patient's clinical syndrome allow for better prediction as to which patient subgroups will benefit from different repair techniques or intervention at all. Most of the techniques are based on surgical technique and are applied as single-device/technique solutions, whether leaflet, chordal, or annular solutions, but with broadening experience, combination therapies are likely to find a place in creating a more complete and surgical-like solution.Signal-induced proliferation-associated protein 1 (SIPA1) is highly expressed and mainly located in the nucleus in some breast cancer cell lines and clinical tumor tissues. Previous study revealed that nuclear localization of SIPA1 is functionally involved in breast cancer metastasis in the lymphatic gland. In the current study, we identified a non-typical region (140-179aa) of SIPA1 as a novel nuclear localization region (NLR) which is crucial for translocating the proteins into the nucleus in HEK293 cells and breast cancer cells. This region contained one basic amino acid, His160, and had no common features of typical nuclear localization signals. In addition, overexpressing SIPA1 without NLR could suppress breast cancer cell proliferation but could not promote cell migration in MCF7 cells. Furthermore, we found that a high expression of SIPA1 upregulated the expression of ABCB1, encoding multi-drug resistance protein MDR1, and promoted the resistance to epirubicin in breast cancer cells, while this effect was largely abolished in the cells with the expression of NLR-deleted SIPA1. This study overall, identified a nuclear localization-dependent region determining the nuclear distribution of SIPA1 and its regulation on epirubicin-sensitivity in breast cancer cells, which could be a potential drug target to facilitate the development of breast cancer chemotherapy.