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The NCATS BioPlanet – An Integrated Platform for Exploring the Universe of Cellular Signaling Pathways for Toxicology, Systems Biology, and Chemical Genomics
We report here the construction, features, and utilization of a comprehensive integrated and non-redundant pathway resource, the NCATS BioPlanet (Figure 1). The resource hosts information only from public sources that have been herein further manually curated to ensure the quality of the data. Along with our pathway warehouse, the NCATS BioPlanet software platform allows easy browsing and visualization of the universe of pathways, and exploration of associations among them. Additionally, we curated the set of annotated pathways in terms of the biological space covered and the current availability of assays, either commerci...
Source: Frontiers in Pharmacology - April 25, 2019 Category: Drugs & Pharmacology Source Type: research

Non-canonical Notch Signaling Regulates Actin Remodeling in Cell Migration by Activating PI3K/AKT/Cdc42 Pathway
In conclusion, our research results indicate that DAPT activates PI3K/AKT/Cdc42 signaling by non-canonical Notch pathway, and the activated Cdc42 promotes the filopodia formation and inhibits lamellipodia assembly, resulting in reduced migration of breast cancer cells. The results imply that non-canonical Notch signaling may play a very important role in the rapid response of cells to the extracellular signals. Author Contributions LG, JD, and LL designed the study and wrote and revised the manuscript. LL and LZ performed most of the experiments and data analysis. SZ, X-YZ, P-XM, Y-DM, Y-YW, YC, S-JT, and Y-JZ assisted i...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

Lipid-based nanocarriers for siRNA delivery: challenges, strategies and the lessons learned from the DODAX:MO liposomal system.
Abstract The possibility of using the RNA interference (RNAi) mechanisms in gene therapy was one of the scientific breakthroughs of the last century. Despite the extraordinary therapeutic potential of this approach, the need for an efficient gene carrier is hampering the translation of the RNAi technology to the clinical setting. Although a diversity of nanocarriers have been described, liposomes continue to be one of the most attractive siRNA vehicles due to their relatively low toxicity, facilitated siRNA complexation, high transfection efficiency and enhanced pharmacokinetic properties. This review focuses on R...
Source: Current Drug Targets - July 3, 2018 Category: Drugs & Pharmacology Authors: Oliveira ACN, Fernandes J, Goncalves A, Gomes AC, Oliveira R Tags: Curr Drug Targets Source Type: research

Current preclinical small interfering RNA (siRNA)-based conjugate systems for RNA therapeutics.
Abstract Recent promising clinical results of RNA therapeutics have drawn big attention of academia and industries to RNA therapeutics and their carrier systems. To improve their feasibility in clinics, systemic evaluations of currently available carrier systems under clinical trials and preclinical studies are needed. In this review, we focus on recent noticeable preclinical studies and clinical results regarding siRNA-based conjugates for clinical translations. Advantages and drawbacks of siRNA-based conjugates are discussed, compared to particle-based delivery systems. Then, representative siRNA-based conjugate...
Source: Advanced Drug Delivery Reviews - October 27, 2015 Category: Drugs & Pharmacology Authors: Lee SH, Kang YY, Jang HE, Mok H Tags: Adv Drug Deliv Rev Source Type: research