247 research outputs found
Therapeutic Applications and Mechanisms of YC-1: A Soluble Guanylate Cyclase Stimulator
Nitric oxide (NO) is an essential endogenous vasodilator to maintain vascular homeostasis, whose effects are mainly mediated by NO-dependent soluble guanylate cyclase (sGC) which catalyzes the synthesis of cyclic guanosine monophosphate (cGMP), a critical mediator of vascular relaxation. YC-1, a novel NO-independent sGC stimulator, was first introduced as an inhibitor of platelet aggregation and thrombosis. Accumulating studies revealed that YC-1 has multiple medication potentials to use for a broad spectrum of diseases ranging from cardiovascular diseases to cancers. In contrast to NO donors, YC-1 has a more favorable safety profile and low medication tolerance. In this chapter, we introduce canonical and pathological roles of NO, review activations, and regulatory mechanisms of YC-1 on NO-independent sGC/cGMP pathway and present the potential pharmacological applications and molecular mechanisms of YC-1
Biclustering random matrix partitions with an application to classification of forensic body fluids
Classification of unlabeled data is usually achieved by supervised learning
from labeled samples. Although there exist many sophisticated supervised
machine learning methods that can predict the missing labels with a high level
of accuracy, they often lack the required transparency in situations where it
is important to provide interpretable results and meaningful measures of
confidence. Body fluid classification of forensic casework data is the case in
point. We develop a new Biclustering Dirichlet Process (BDP), with a
three-level hierarchy of clustering, and a model-based approach to
classification which adapts to block structure in the data matrix. As the class
labels of some observations are missing, the number of rows in the data matrix
for each class is unknown. The BDP handles this and extends existing
biclustering methods by simultaneously biclustering multiple matrices each
having a randomly variable number of rows. We demonstrate our method by
applying it to the motivating problem, which is the classification of body
fluids based on mRNA profiles taken from crime scenes. The analyses of
casework-like data show that our method is interpretable and produces
well-calibrated posterior probabilities. Our model can be more generally
applied to other types of data with a similar structure to the forensic data.Comment: 45 pages, 10 figure
Effects of Salvianolic Acid B on Protein Expression in Human Umbilical Vein Endothelial Cells
Salvianolic acid B (Sal B), a pure water-soluble compound extracted from Radix Salviae miltiorrhizae, has been reported to possess potential cardioprotective efficacy. To identify proteins or pathways by which Sal B might exert its protective activities on the cardiovascular system, two-dimensional gel electrophoresis-based comparative proteomics was performed, and proteins altered in their expression level after Sal B treatment were identified by MALDI-TOF MS/MS. Human umbilical vein endothelial cells (HUVECs) were incubated at Sal B concentrations that can be reached in human plasma by pharmacological intervention. Results indicated that caldesmon, an actin-stabilizing protein, was downregulated in Sal B-exposed HUVECs. Proteins that showed increased expression levels upon Sal B treatment were vimentin, T-complex protein 1, protein disulfide isomerase, tropomyosin alpha, heat shock protein beta-1, UBX domain-containing protein 1, alpha enolase, and peroxiredoxin-2. Additionally, Sal B leads to increased phosphorylation of nucleophosmin in a dose-dependent manner and promotes proliferation of HUVECs. We found that Sal B exhibited a coordinated regulation of enzymes and proteins involved in cytoskeletal reorganization, oxidative stress, and cell growth. Our investigation would provide understanding to the endothelium protection information of Sal B
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