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Total 19 results found since Jan 2013.

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

REGULATION OF OVULATORY GENES IN BOVINE GRANULOSA CELLS: LESSONS FROM siRNA SILENCING OF PTGS2.
Abstract Prostaglandin endoperoxide synthase 2 (PTGS2), tumor necrosis factor-alpha-induced protein-6 (TNFAIP6), pentraxin-3 (PTX3), epidermal growth factor like factors: amphiregulin (AREG) and epiregulin (EREG) are essential for successful ovulation. We compared here the induction of these ovulatory genes in bovine granulosa cells (GCs) in vivo (after LH surge) and in vitro (forskolin treatment). These genes were markedly stimulated in GCs isolated from cows 21hr after LH- surge. In isolated GCs, forskolin induced a distinct temporal profile for each gene. Generally, there was a good agreement between the in viv...
Source: Reproduction - October 16, 2014 Category: Reproduction Medicine Authors: Shrestha K, Lukasik K, Baufeld A, Vanselow J, Moallem U, Meidan R Tags: Reproduction Source Type: research

Regulation of ovulatory genes in bovine granulosa cells: lessons from siRNA silencing of PTGS2
In this study, we compared the induction of these ovulatory genes in bovine granulosa cells (GCs) in vivo (after LH surge) and in vitro (forskolin (FRS) treatment). These genes were markedly stimulated in GCs isolated from cows 21 h after LH-surge. In isolated GCs, FRS induced a distinct temporal profile for each gene. Generally, there was a good agreement between the in vivo and in vitro inductions of these genes except for PTX3. Lack of PTX3 induction in isolated GCs culture suggests that other follicular compartments may mediate its induction by LH. Next, to study the role of PTGS2 and prostaglandins (PGs) in the cascad...
Source: Reproduction - November 28, 2014 Category: Reproduction Medicine Authors: Shrestha, K., Lukasik, K., Baufeld, A., Vanselow, J., Moallem, U., Meidan, R. Tags: Research 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

Implementing an Innovative Lipid Management Technique Using siRNA LDL-C Lowering Therapy: Lessons Learned in an NHS Primary Care Practice With Worked Case Examples
CONCLUSIONS: Enhanced lipid management as a secondary prevention measure is achievable in line with national guidance and objectives. The methodology and education/training processes used in combination with reconstructing the management process can help practice staff realize the program benefits, which in turn can lead to a shift in behavior where all staff embed manual case-finding of high-risk patients into everyday consultations and reviews; enabling rapid identification of eligible patients. Taking a multi-disciplinary, holistic approach to new initiatives reduces service burden, particularly for GPs. Leveraging reso...
Source: Primary Care - May 16, 2023 Category: Primary Care Authors: Carl Deaney Meredith Donaldson Agne Meskauskiene Source Type: research

Lessons from SARS and MERS remind us of the possible therapeutic effects of implementing a siRNA strategy to target COVID-19: Shoot the messenger!
PMID: 32677763 [PubMed - as supplied by publisher]
Source: J Cell Mol Med - July 16, 2020 Category: Molecular Biology Authors: Habtemariam S, Berindan-Neagoe I, Cismaru CA, Schaafsma D, Nabavi SF, Ghavami S, Banach M, Nabavi SM Tags: J Cell Mol Med 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

Immune-Modulation by the Human Respiratory Syncytial Virus: Focus on Dendritic Cells
This study is complemented by another report that found that hRSV infection induces significant expression of three miRNAs, namely hsa-miR-4448, hsa-miR-30a-5p, and hsa-miR-4634 in human DCs (104). Interestingly, this latter study also performed comparative analyses of miRNA profiles between DCs infected with hRSV and a related virus, namely the human metapneumovirus, and found that both viruses induced the expression of elevated levels of hsa-miR-4634. Elucidating the contribution of these miRNAs in DCs in response to hRSV remains to be determined. Dendritic Cell Phenotype and Migration Upon hRSV Infection in vivo Altho...
Source: Frontiers in Immunology - April 14, 2019 Category: Allergy & Immunology Source Type: research

A Novel Regulator of Preadipocyte Differentiation, Transcription Factor TCF21, Functions Partially Through Promoting LPL Expression
Discussion Excessive fat deposition in chickens can result in many undesirable consequences within the poultry industry, including reduced feeding efficiency (Zhou et al., 2006) and decreased reproductive performance (Walzem and Chen, 2014). Thus, broiler breeders urgently require a more thorough understanding of the molecular mechanism governing chicken adipogenesis. We previously found that broilers from lean and fat lines exhibit clear differences in reproductive performance (Zhang et al., 2018). In addition, TCF21 was found to be related to testis growth and development in these broilers (Zhang et al., 2017). In mice ...
Source: Frontiers in Physiology - April 22, 2019 Category: Physiology Source Type: research

Imaging Functional Nucleic Acid Delivery to Skin
Monogenic skin diseases arise from well-defined single gene mutations, and in some cases a single point mutation. As the target cells are superficial, these diseases are ideally suited for treatment by nucleic acid-based therapies as well as monitoring through a variety of noninvasive imaging technologies. Despite the accessibility of the skin, there remain formidable barriers for functional delivery of nucleic acids to the target cells within the dermis and epidermis. These barriers include the stratum corneum and the layered structure of the skin, as well as more locally, the cellular, endosomal and nuclear membranes. A ...
Source: Springer protocols feed by Imaging/Radiology - October 11, 2015 Category: Radiology Source Type: news

Lymphoblastoid Cell Lines Models of Drug Response: Successes and Lessons from This Pharmacogenomic Model.
Abstract A new standard for medicine is emerging that aims to improve individual drug responses through studying associations with genetic variations. This field, pharmacogenomics, is undergoing a rapid expansion due to a variety of technological advancements that are enabling higher throughput with reductions in cost. Here we review the advantages, limitations, and opportunities for using lymphoblastoid cell lines (LCL) as a model system for human pharmacogenomic studies. There are a wide range of publicly available resources with genome-wide data available for LCLs from both related and unrelated populations, re...
Source: Current Molecular Medicine - August 11, 2014 Category: Molecular Biology Authors: Jack J, Rotroff D, Motsinger-Reif AA Tags: Curr Mol Med Source Type: research

Aurin Causes Lethal Proteotoxic Stress in Melanoma Cells Signal Transduction
Pharmacological induction of proteotoxic stress is rapidly emerging as a promising strategy for cancer cell-directed chemotherapeutic intervention. Here, we describe the identification of a novel drug-like heat shock response inducer for the therapeutic induction of proteotoxic stress targeting malignant human melanoma cells. Screening a focused library of compounds containing redox-directed electrophilic pharmacophores employing the Stress 4-[bis(p-hydroxyphenyl)methylene]-2,5-cyclohexadien-1-one) was identified as an experimental cell stress modulator that causes (i) heat shock factor transcriptional activation, (ii) up-...
Source: Journal of Biological Chemistry - January 16, 2015 Category: Chemistry Authors: Davis, A. L., Qiao, S., Lesson, J. L., Rojo de la Vega, M., Park, S. L., Seanez, C. M., Gokhale, V., Cabello, C. M., Wondrak, G. T. Tags: Cell Biology Source Type: research

ABCB1 Is Upregulated in Acquisition of Taxane Resistance: Lessons from Esophageal Squamous Cell Carcinoma Cell Lines.
In conclusion, we propose that ABCB1 might play a pivotal role in acquisition of taxane resistance and could be a promising target for treatment of patients with esophageal cancer after acquisition of taxane resistance. PMID: 27941276 [PubMed - in process]
Source: The Tohoku Journal of Experimental Medicine - December 14, 2016 Category: Research Authors: Wang R, Sumarpo A, Saiki Y, Chen N, Sunamura M, Horii A Tags: Tohoku J Exp Med Source Type: research

Abstract P2-11-02: A longitudinal look at toxicity management within a platform trial: Lessons from the I-SPY 2 TRIAL
In this study, we performed siRNA-mediated knockdown to determine the importance of SHC1 and NCOA3 in the cell proliferation and death of TNBC. The effect of siSHC1 or siNCOA3 on the invasion and chemoresistance was also assayed in vitro. We found that although SHC1 and NCOA3 knockdown slightly inhibited the tumor growth of TNBC cells (MDA-MB-231, BT549, and HS578T), siSHC1 + paclitaxel and siNCOA3 + paclitaxel significantly decreased cell proliferation and increased caspase-3/7 activity in vitro, compared to drug alone. In vivo studies using MDA-MB-231 xenografts and a TNBC PDX model also showed that siSHC1 and siNCOA3 si...
Source: Cancer Research - February 13, 2017 Category: Cancer & Oncology Authors: M Paoloni, J Lyandres, MB Buxton, DA Berry, LJ Esserman, A DeMichele, D Yee Tags: Poster Session Abstracts Source Type: research