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Chimeric flaviviral RNA-siRNA molecules resist degradation by the exoribonuclease Xrn1 and trigger gene silencing in mammalian cells
Chembiochem. 2021 Aug 25. doi: 10.1002/cbic.202100434. Online ahead of print.ABSTRACTRNA is an emerging platform for drug delivery, but the susceptibility of RNA to nuclease degradation remains a major barrier to its implementation in vivo. Here, we engineered flaviviral Xrn1-resistant RNA (xrRNA) motifs to host small interfering RNA (siRNA) duplexes. The xrRNA-siRNA molecules self-assemble in vitro, resist degradation by the conserved eukaryotic 5' to 3' exoribonuclease Xrn1, and trigger gene silencing in 293T cells. The resistance of the molecules to Xrn1 does not translate to stability in blood serum. Nevertheless, our ...
Source: Chembiochem - August 25, 2021 Category: Biochemistry Authors: Cressida Harvey Sven Klassa Esteban Finol Jonathan Hall Alyssa Hill Source Type: research

Evaluation of an Integrin αvβ3 Radiotracer, 18FF-FPP-RGD2, for Monitoring Pharmacological Effects of Integrin αv siRNA in the NASH Liver
ConclusionThis study suggests that [18F]F-FPP-RGD2 PET imaging is a promising radiotracer for monitoring hepatic integrin αv protein levels and hepatic function in NASH pathology.
Source: Nuclear Medicine and Molecular Imaging - March 7, 2023 Category: Nuclear Medicine Source Type: research

Effect of siRNA-mediated knockdown of eIF3c gene on survival of colon cancer cells.
This study was focused on investigating the effect of small interfering RNA (siRNA)-mediated eIF3c gene knockdown on colon cancer cell survival. The eIF3c gene was observed to be highly expressed in colon cancer cell models. The expression levels of the gene in eIF3c siRNA infected and control siRNA infected cells were compared via real-time polymerase chain reaction (PCR) and western blotting analysis. Cell proliferation levels were analyzed employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. Furthermore, the effects of eIF3c gene knockdown on the cell cycle and apopto...
Source: J Zhejiang Univ Sci ... - June 1, 2013 Category: Science Authors: Song N, Wang Y, Gu XD, Chen ZY, Shi LB Tags: J Zhejiang Univ Sci B Source Type: research

High efficacy gold-KDEL peptide-siRNA nanoconstruct-mediated transfection in C2C12 myoblasts and myotubes
Abstract: Gold nanoparticles (AuNP) were conjugated with cysteine terminated KDEL (Lys-Asp-Glu-Leu) peptide and siRNA directed against NADPH Oxidase 4 (Nox4). Fluorescence microscopy analysis provided evidence of cytocellular retrograde transport pathways and sub-cellular colocalization of AuNP nanoconstructs in both undifferentiated C2C12 myoblasts and differentiated C2C12 myotubes. The cellular trafficking of AuNP nanoconstructs in undifferentiated myoblasts suggests stable and efficient transfection of siRNA as demonstrated by colocalization of AuNP-delivered KDEL and siRNA. The cellular uptake of AuNP nanoconstructs wa...
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - August 8, 2013 Category: Nanotechnology Authors: Suresh Acharya, Rodney Allan Hill Tags: Cell Biology, Intracellular Transport Mechanism, Sirna-Au-KDEL Peptide Nanoconstructs Source Type: research

i-Fect, BDNF and Irritable Bowel Syndrome (IBS)
Conclusion: Chronic prenatal stress followed by a second exposure to HeICS in adult offspring exacerbated visceral hypersensitivity (VHS) greater in female offspring that persisted longer than in male offspring. Chronic prenatal stress up-regulated BDNF expression in the lumbar-sacral dorsal horn that correlated with the exacerbation of VHS in female, but not in male offspring by increasing RNA Pol II binding and histone H3 acetylation, and decreasing histone deacetylase 1 association with the core promoter of BDNF in female offspring.
Source: siRNA and DsiRNA Transfection Efficiency - March 11, 2014 Category: Neuroscience Tags: BDNF;chronic stress;functional bowel disorders;iritable bowel syndrome;visceral hypersnsitivity i-Fect intrathecal delivery of siRNA Source Type: news

Preclinical development of siRNA therapeutics: Towards the match between fundamental science and engineered systems
Abstract: The evolution of synthetic RNAi faces the paradox of interfering with the human biological environment. Due to the fact that all cell physiological processes can be target candidates, silencing a precise biological pathway could be challenging if target selectivity is not properly addressed. Molecular biology has provided scientific tools to suppress some of the most critical issues in gene therapy, while setting the standards for siRNA clinical application. However, the protein down-regulation through the mRNA silencing is intimately related to the sequence-specific siRNA ability to interact accurately with the ...
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - December 11, 2013 Category: Nanotechnology Authors: M. Videira, A. Arranja, D. Rafael, R. Gaspar Tags: Cell Biology and Genetics, Amino Acids, Nucleic Acids, siRNA Therapy, Basic Science vs. Engineering Source Type: research

EPO Protects Against Cerebral Ischemia
In this study data suggest the protective effects of EPO on NUV injuries are highly associated with the increase of p-Cx43, which improves GJIC to reduce neurotoxic substances: Ziyi Zhoua, Xiaobai Weib, Jun Xiang, Junpeng Gao, Lixin Wang, Jinsong You, Yefeng Cai , Dingfang Caid. Protection of erythropoietin against ischemic neurovascular unit injuries through the effects of connexin43. Biochemical and Biophysical Research Communications. doi:10.1016/j.bbrc.2015.02...The strands were incubated at 90°C for 5 min and then at 37°C for 1 h. SiRNA was prepared immediately before administration by mixing the RNA solution (1 μg...
Source: siRNA and DsiRNA Transfection Efficiency - February 18, 2015 Category: Neuroscience Tags: cerebral ischemia Connexin 43 Delivering siRNA to the CNS i-Fect iFect siRNA transfection of neurons Source Type: news

siRNA Delivery Impedes the Temporal Expression of Cytokine-Activated VCAM1 on Endothelial Cells.
Abstract Leukocyte recruitment plays a key role in chronic inflammatory diseases such as cardiovascular disease, rheumatoid arthritis, and cancer. Leukocyte rolling and arrest are mediated in part by the temporally-regulated surface expression of vascular cell adhesion molecule-1 (VCAM1) on endothelial cells (ECs). In this paper, we engineered a pH-responsive vehicle comprised of 30 mol% dimethylaminoethyl methacrylate (30D) and 70 mol% hydroxyethyl methacrylate (70H) to encapsulate, protect, and deliver VCAM1 small interfering RNA (siRNA). The ability of siRNA to reduce VCAM1 gene expression is in direct opposi...
Source: Annals of Biomedical Engineering - June 23, 2015 Category: Biomedical Engineering Authors: Ho TT, You JO, Auguste DT Tags: Ann Biomed Eng Source Type: research

High Sensitivity RT-qPCR Assay of Nonlabeled siRNA in Small Blood Volume for Pharmacokinetic Studies: Application to Survivin siRNA
Abstract RNAi therapeutics provide an opportunity to correct faulty genes, and several RNAi have entered clinical evaluation. The existing quantification methods typically use radioactivity- or fluorescence-labeled RNAi, require large blood volumes, and/or have a limited dynamic detection range. We established a quantitative reverse transcriptase real-time polymerase chain reaction (RT-qPCR) assay to measure RNAi; the model analyte was survivin siRNA (siSurvivin). A second siRNA was used as the internal standard. The three major steps were (a) extraction of the two siRNAs from blood or water, (b) synthesis of the...
Source: The AAPS Journal - October 24, 2015 Category: Drugs & Pharmacology Source Type: research

Exosomes from iPSCs Delivering siRNA Attenuate Intracellular Adhesion Molecule-1 Expression and Neutrophils Adhesion in Pulmonary Microvascular Endothelial Cells
In this study, we reprogrammed urine exfoliated renal epithelial cells into human induced pluripotent stem cells (huiPSCs) and purified the exosomes (Exo) from huiPSCs as RNAi delivery system. Through choosing the episomal system to deliver transcription factors, we obtained a non-integrating huiPSCs. Experiments in bothvitro andvivo demonstrated that these huiPSCs possess the pluripotent properties. The exosomes of huiPSCs isolated by differential centrifugation were visualized by transmission electron microscopy (TEM) showing a typical exosomal appearance with an average diameter of 122  nm. Immunoblotting confirmed the...
Source: Inflammation - December 20, 2016 Category: Allergy & Immunology Source Type: research

Sequential therapy with redox-responsive glucolipid nanocarrier separately delivering siRNA and doxorubicin to overcome multidrug resistance
Publication date: 20 December 2017 Source:International Journal of Pharmaceutics, Volume 534, Issues 1–2 Author(s): Tingting Meng, Binbin Lu, Shihong Shao, Ming Yuan, Xuan Liu, Hong Yuan, Xuan Huang, Fuqiang Hu P-glycoprotein (P-gp) is a major efflux transporter overexpressed on multidrug resistant tumor cells and responsible for pumping drugs out. If anti-tumor drugs are given when P-gp level is low, satisfactory treatment efficiency may be achieved. Thus, a P-gp down-regulating siRNA (siMDR1) and doxorubicin (DOX) were applied to eliminate multidrug resistant breast cancer cells (MCF-7/ADR). A redox-responsive glucoli...
Source: International Journal of Pharmaceutics - November 6, 2017 Category: Drugs & Pharmacology Source Type: research

SiRNA interfering STAT3 enhances DDP sensitivity in cervical cancer cells.
CONCLUSIONS: STAT3 over-expression is associated with DDP resistance in cervical cancer. Decreasing STAT3 can significantly promote the apoptosis of cervical cancer CaSki cells and decrease the DDP resistance. PMID: 30024597 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - July 20, 2018 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

Patient-based benefit-risk assessment of medicines: development, refinement, and validation of a content search strategy to retrieve relevant studies
J Med Libr Assoc. 2022 Apr 1;110(2):185-204. doi: 10.5195/jmla.2022.1306.ABSTRACTINTRODUCTION: Poor indexing and inconsistent use of terms and keywords may prevent efficient retrieval of studies on the patient-based benefit-risk assessment (BRA) of medicines. We aimed to develop and validate an objectively derived content search strategy containing generic search terms that can be adapted for any search for evidence on patient-based BRA of medicines for any therapeutic area.METHODS: We used a robust multistep process to develop and validate the content search strategy: (1) we developed a bank of search terms derived from s...
Source: J Med Libr Assoc AND... - April 20, 2022 Category: Databases & Libraries Authors: Hiba El Masri Treasure M McGuire Christine Dalais Mieke van Driel Helen Benham Samantha A Hollingworth Source Type: research