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Total 328 results found since Jan 2013.

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

5'-triphosphate-siRNA activates RIG-I-dependent type I interferon production and enhances inhibition of hepatitis B virus replication in HepG2.2.15 cells.
In conclusion, our findings suggest that 3p-siRNA could act as a powerful bifunctional antiviral molecule with potential for developing a promising therapeutic against chronic HBV infection. PMID: 24099962 [PubMed - as supplied by publisher]
Source: European Journal of Pharmacology - October 4, 2013 Category: Drugs & Pharmacology Authors: Chen X, Qian Y, Yan F, Tu J, Yang X, Xing Y, Chen Z Tags: Eur J Pharmacol Source Type: research

Imaging and therapy of liver fibrosis using bioreducible polyethylenimine/siRNA complexes conjugated with N-acetylglucosamine as a targeting moiety.
Abstract Diagnosis and therapy of early stage liver fibrosis is very important for the treatment of fatal liver diseases. Here, we report on the targeted imaging and therapy of activated hepatic stellate cells (HSCs) and fibrotic liver tissue using N-acetylglucosamine (GlcNAc)- and indocyanine green (ICG)-conjugated PEI/siRNA complexes. The conjugation of a disulfide bond to PEI (PEI-D) was achieved by Michael addition. We modified PEI with N-acetylglucosamine (PEI-D-GlcNAc), which can specifically interact with desmin on activated HSCs, using the EDC coupling method. Confocal microscopic analysis showed that the ...
Source: Biomaterials - May 28, 2013 Category: Materials Science Authors: Kim SJ, Ise H, Kim E, Goto M, Akaike T, Chung BH Tags: Biomaterials Source Type: research

Ionizable Amphiphilic Dendrimer-Based Nanomaterials with Alkyl-Chain-Substituted Amines for Tunable siRNA Delivery to the Liver Endothelium In Vivo.
Abstract A library of dendrimers was synthesized and optimized for targeted small interfering RNA (siRNA) delivery to different cell subpopulations within the liver. Using a combinatorial approach, a library of these nanoparticle-forming materials was produced wherein the free amines on multigenerational poly(amido amine) and poly(propylenimine) dendrimers were substituted with alkyl chains of increasing length, and evaluated for their ability to deliver siRNA to liver cell subpopulations. Interestingly, two lead delivery materials could be formulated in a manner to alter their tissue tropism within the liver-with...
Source: Angewandte Chemie - October 29, 2014 Category: Chemistry Authors: Khan OF, Zaia EW, Yin H, Bogorad RL, Pelet JM, Webber MJ, Zhuang I, Dahlman JE, Langer R, Anderson DG Tags: Angew Chem Int Ed Engl Source Type: research

Inhibition of hepatitis C virus using siRNA targeted to the virus and Hsp90.
Abstract Hepatitis C (HCV) is a viral disease affecting millions of people worldwide, and persistent HCV infection can lead to progressive liver disease with the development of liver cirrhosis and hepatocellular carcinoma. During treatment for hepatitis C, the occurrence of viral resistance is common. To reduce the occurrence of resistance, new viral treatments should target both viral and cellular factors. Many interactions occur between viral and host proteins during the HCV replication cycle and might be used for the development of new therapies against hepatitis C. Heat shock protein 90 (Hsp90) plays a role in...
Source: Cell Stress and Chaperones - November 16, 2016 Category: Cytology Authors: Braga AC, Carneiro BM, Batista MN, Akinaga MM, Rahal P Tags: Cell Stress Chaperones Source Type: research

CD98 siRNA-loaded nanoparticles decrease hepatic steatosis in mice
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid hepatic accumulation. Here, we investigated whether a reduction of CD98 expression mediated by CD98 siRNA-loaded nanoparticles (NPs) could attenuate liver disease markers in a mouse model of NAFLD. NPs were generated using a double emulsion/solvent evaporation technique. Mice fed a high fat diet for 8 weeks to induce fatty liver were treated with vein tail injections of CD98 siRNA-loaded NPs. In vitro, HepG2 treated with CD98 siRNA-loaded NPs showed significant downregulation of CD98 leading to a significant decrease of major pro-inflammatory cytokines and markers.
Source: Digestive and Liver Disease - November 16, 2016 Category: Gastroenterology Authors: Brandon S.B. Canup, Heliang Song, Vu Le Ngo, Xiangxiao Meng, Timothy L. Denning, Pallavi Garg, Hamed Laroui Tags: Liver, Pancreas and Biliary Tract Source Type: research

Lipid-encapsulated siRNA for hepatocyte-directed treatment of advanced liver disease
Cell Death & Disease, Published online: 11 May 2020; doi:10.1038/s41419-020-2571-4Lipid-encapsulated siRNA for hepatocyte-directed treatment of advanced liver disease
Source: Cell death and disease - May 10, 2020 Category: Internal Medicine Authors: Marius Maximilian Woitok Miguel Eugenio Zoubek Dennis Doleschel Matthias Bartneck Mohamed Ramadan Mohamed Fabian Kie ßling Wiltrud Lederle Christian Trautwein Francisco Javier Cubero Source Type: research

Title: Genistein Disrupts Glucocorticoid Receptor Signaling in Human Uterine Endometrial Ishikawa Cells
Conclusions: Using Ishikawa cells, we observed that exposure to genistein resulted in distinct changes in gene expression and unique differences in the GR transcriptome. Citation: Whirledge S, Senbanjo LT, Cidlowski JA. 2015. Genistein disrupts glucocorticoid receptor signaling in human uterine endometrial Ishikawa cells. Environ Health Perspect 123:80–87; http://dx.doi.org/10.1289/ehp.1408437 Address correspondence to J.A. Cidlowski, NIH/NIEHS, MD F3-07, P.O. Box 12233, Research Triangle Park, NC 27709 USA. Telephone: (919) 541-1564. E-mail: cidlows1@niehs.nih.gov We thank X. Xu (Integrative Bioinformatic...
Source: EHP Research - December 31, 2014 Category: Environmental Health Authors: Web Admin Tags: Research Article January 2015 Source Type: research

Tangshen Formula Alleviates Hepatic Steatosis by Inducing Autophagy Through the AMPK/SIRT1 Pathway
Conclusion In conclusion, the present study demonstrated that autophagy was involved in relieving the effects of TSF against NAFLD, which were mediated by the AMPK/SIRT1 pathway (Figure 7D). These findings may improve our current understanding of the role of TSF in treating hepatic steatosis and provide an experimental basis for the clinical application of TSF in NAFLD and its related metabolic syndrome. Ethics Statement This study was carried out in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Ethics Co...
Source: Frontiers in Physiology - April 25, 2019 Category: Physiology Source Type: research

Viruses, Vol. 14, Pages 2052: Oligonucleotide-Based Therapies for Chronic HBV Infection: A Primer on Biochemistry, Mechanisms and Antiviral Effects
t Three types of oligonucleotide-based medicines are under clinical development for the treatment of chronic HBV infection. Antisense oligonucleotides (ASOs) and synthetic interfering RNA (siRNA) are designed to degrade HBV mRNA, and nucleic acid polymers (NAPs) stop the assembly and secretion of HBV subviral particles. Extensive clinical development of ASOs and siRNA for a variety of liver diseases has established a solid understanding of their pharmacodynamics, accumulation in different tissue types in the liver, pharmacological effects, off-target effects and how chemical modifications and delivery approaches affect...
Source: Viruses - September 16, 2022 Category: Virology Authors: Andrew Vaillant Tags: Review Source Type: research

Placental growth factor silencing ameliorates liver fibrosis and angiogenesis and inhibits activation of hepatic stellate cells in a murine model of chronic liver disease.
This study aimed to assess the effect of reducing PlGF expression using small interfering RNA (siRNA) on experimental liver fibrosis and angiogenesis, and to elucidate the underlying molecular mechanisms. Fibrosis was induced in mice by carbon tetrachloride (CCl4 ) for 8 weeks, and mice were treated with PlGF siRNA or non-targeting control siRNA starting two weeks after initiating CCl4 injections. The results showed that PlGF was highly expressed in cirrhotic human and mice livers; which mainly distributed in activated hepatic stellate cells (HSCs). PlGF silencing robustly reduced liver inflammation, fibrosis, intrahepatic...
Source: J Cell Mol Med - April 5, 2017 Category: Molecular Biology Authors: Li X, Yao QY, Liu HC, Jin QW, Xu BL, Zhang SC, Tu CT Tags: J Cell Mol Med Source Type: research

Placental growth factor silencing ameliorates liver fibrosis and angiogenesis and inhibits activation of hepatic stellate cells in a murine model of chronic liver disease
This study aimed to assess the effect of reducing PlGF expression using small interfering RNA (siRNA) on experimental liver fibrosis and angiogenesis, and to elucidate the underlying molecular mechanisms. Fibrosis was induced in mice by carbon tetrachloride (CCl4) for 8 weeks, and mice were treated with PlGF siRNA or non‐targeting control siRNA starting two weeks after initiating CCl4 injections. The results showed that PlGF was highly expressed in cirrhotic human and mice livers; which mainly distributed in activated hepatic stellate cells (HSCs). PlGF silencing robustly reduced liver inflammation, fibrosis, intrahepati...
Source: Journal of Cellular and Molecular Medicine - April 1, 2017 Category: Molecular Biology Authors: Xi Li, Qun ‐Yan Yao, Hong‐Chun Liu, Qian‐Wen Jin, Bei‐Li Xu, Shun‐Cai Zhang, Chuan‐Tao Tu Tags: Original Article Source Type: research

Evaluation of the Consequence of CTNNB1 & amp; RAB1A Targeting on Hepatocellular Carcinoma Cell Line
ConclusionTargetingCTNNB1or RAB1A in HepG2 cell lines decreased the cell viability and proliferative activity. Moreover, targetingCTNNB1 was effective in decreasing cell proliferative activity compared to targetingRAB1A in HepG2 cell lines. So, targeting CTNNB1 may have a potential therapeutic effect in treatment of HCC.
Source: QJM - October 1, 2021 Category: Internal Medicine Source Type: research

RNAi Therapeutics for Diseases Involving Protein Aggregation: Fazirsiran for Alpha-1 Antitrypsin Deficiency-associated Liver Disease
This article describes the role of misfolded proteins and protein aggregates in disease, and options for therapeutic approaches. The RNAi mechanism is discussed, along with how the siRNA therapeutic fazirsiran for the treatment of AATD was developed. We also describe implications of siRNA therapeutics in extrahepatic diseases.EXPERT OPINION: Using RNAi as a therapeutic approach is well suited to treat disease in conditions where an excess of a protein or the effect of an abnormal mutated protein causes disease. The results observed for the first few siRNA therapeutics that were approved or are in development provide an imp...
Source: Expert Opinion on Investigational Drugs - July 20, 2023 Category: Drugs & Pharmacology Authors: Pavel Strnad Javier San Martin Source Type: research