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Current Development of siRNA Bioconjugates: From Research to the Clinic
In this study, it was shown that the main factor determining the nature of the biodistribution of conjugates is their lipophilicity. Conjugates of siRNA with lower lipophilicity; i.e., derivatives of retinoic acid, lithocholic acid, and docosahexanoic acid with greater efficiency than cholesterol conjugates accumulated in the kidneys, bladder, and lungs of the mouse after subcutaneous injection (Biscans et al., 2018). This fact is consistent with previous data that showed that more lipophilic conjugates bind more efficiently to serum components, and thus are not excreted by the kidneys (Wolfrum et al., 2007; Osborn et al.,...
Source: Frontiers in Pharmacology - April 25, 2019 Category: Drugs & Pharmacology Source Type: research

Molecular Mechanisms in Clear Cell Renal Cell Carcinoma: Role of miRNAs and Hypermethylated miRNA Genes in Crucial Oncogenic Pathways and Processes
Eleonora A. Braga1*†, Marina V. Fridman2†, Vitaly I. Loginov1,3, Alexey A. Dmitriev4 and Sergey G. Morozov1 1Institute of General Pathology and Pathophysiology, Moscow, Russia 2Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia 3Research Center of Medical Genetics, Moscow, Russia 4Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer, and it has the highest mortality rate. The increasing drug resistance of metastatic ccRCC has resulted in the search f...
Source: Frontiers in Genetics - April 23, 2019 Category: Genetics & Stem Cells Source Type: research

Ability to Suppress TGF- β-Activated Myofibroblast Differentiation Distinguishes the Anti-pulmonary Fibrosis Efficacy of Two Danshen-Containing Chinese Herbal Medicine Prescriptions
Conclusion: This study suggests that a clinically efficacious cardiovascular Chinese herbal medicine (DLP) can be successfully repurposed to treat a lung disease in pulmonary fibrosis guided by TCM theory. Our comparative study between DLP and DHP demonstrated a critical requirement of suppressing both pro-inflammatory and pro-fibrotic pathways for the treatment of pulmonary fibrosis, supporting that a multi-component prescription capable of “removing both phlegm and blood stasis” will better achieve co-protection of heart and lung in PHD. Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic ...
Source: Frontiers in Pharmacology - April 23, 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

Hepatoma-Derived Growth Factor and DDX5 Promote Carcinogenesis and Progression of Endometrial Cancer by Activating β-Catenin
Conclusion: Our results provide novel evidence that HDGF interacts with DDX5 and promotes the progression of EC through the induction of β-catenin. Introduction Endometrial cancer (EC) comprises the most common malignancy involving the female genital tract and the fourth most common malignancy in women after breast, lung, and colorectal cancers (1). In 2012, approximately 320,000 new cases of EC were diagnosed worldwide and the incidence is increasing (2). Currently, endometrial carcinogenesis is thought to be a multi-step process involving the coordinated interaction of hormonal regulation, gene mutation, ad...
Source: Frontiers in Oncology - April 10, 2019 Category: Cancer & Oncology Source Type: research

Selective NP delivery to cancer over normal cells Engineering
Conventional chemotherapeutics nonselectively kill all rapidly dividing cells, which produces numerous side effects. To address this challenge, we report the discovery of functional polyesters that are capable of delivering siRNA drugs selectively to lung cancer cells and not to normal lung cells. Selective polyplex nanoparticles (NPs) were identified by high-throughput...
Source: Proceedings of the National Academy of Sciences - September 26, 2016 Category: Science Authors: Yan, Y., Liu, L., Xiong, H., Miller, J. B., Zhou, K., Kos, P., Huffman, K. E., Elkassih, S., Norman, J. W., Carstens, R., Kim, J., Minna, J. D., Siegwart, D. J. Tags: PNAS Plus Source Type: research