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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

Effect of Inducible Co-Stimulatory Molecule siRNA in Cerebral Infarction Rat Models.
CONCLUSIONS ICOS siRNA can protect brain tissues from ischemia injuries after cerebral infarction, improve limb movement and coordination, lower the mortality rate of rats, and inhibit T cell-induced cytokines. These results collectively suggest the potential treatment efficacy of ICOS siRNA against cerebral infarction. PMID: 26436531 [PubMed - as supplied by publisher]
Source: Medical Science Monitor - October 6, 2015 Category: Research Tags: Med Sci Monit Source Type: research

The Search for the Elusive Elixir of Life
By TOM EMERICK Here’s the executive summary: Most disease and health spending is age-related. As we age we get infirmities ranging from dementia to cancer to vascular disease. Nothing can prevent aging. Period. For millennia mankind has been been on a futile search to prevent aging. Search for the Elusive Elixir of Life For 3500 or more years mankind has been searching for the mythological Elixir of Life, the fountain of youth, the philosophers stone, pool of nectar, etc, that will defeat aging and extend life, if not achieve immortality. According to Wiki, “The elixir of life, also known as the elixir of immortality a...
Source: The Health Care Blog - February 4, 2016 Category: Consumer Health News Authors: Simon Nath Tags: THCB Tom Emerick Source Type: blogs

New Paradigms on siRNA Local Application.
Abstract Small interfering RNA (siRNA) functions through pairing with specific mRNA sequences and results in mRNA degradation, which is becoming a potential therapeutic approach for many diseases caused by altered gene expression. The delivery is a major problem for siRNA application due to its rapid degradation in blood circulation. Various strategies have been proposed to help cellular uptake of siRNA/short or small hairpin RNA (shRNA) successfully. Here we reviewed the recent published data regarding local applications of siRNA. Compared with systematic delivery methods, local delivery of siRNA/shRNA demonstrat...
Source: BMB Reports - July 31, 2014 Category: Biochemistry Authors: Pan M, Ni J, He H, Gao S, Duan X Tags: BMB Rep Source Type: research

Multilevel chitosan-gelatin particles loaded with P4HA1 siRNA suppress glioma development
Drug Deliv Transl Res. 2023 Sep 4. doi: 10.1007/s13346-023-01422-8. Online ahead of print.ABSTRACTIt has been reported that prolyl 4-hydroxylase subunit alpha 1 (P4HA1) promoted tumor growth and metastasis of glioma; thus, targeting P4HA1 may be a promising therapeutic strategy against glioma. In consideration of the instability of siRNA in vivo, the chitosan-gelatin microspheres loaded with P4HA1 siRNA (P4HA1 siRNA@CGM) were employed. Firstly, the gel electrophoresis and hemolytic test were performed to assess the stability and blood compatibility of P4HA1 siRNA@CGM. Then, methyl thiazolyl tetrazolium (MTT), cell colony f...
Source: Cell Research - September 4, 2023 Category: Cytology Authors: Yiting Zhou Jiajia Tian Yi Zhu Yating Zhang Xudong Zhao Source Type: research

Combination of B7H6-siRNA and temozolomide synergistically reduces stemness and migration properties of glioblastoma cancer cells
This study aimed to understand the potential role and molecular mechanism of the combination therapy of B7H6-siRNA and temozolomide in glioblastoma cancer. U87 cells were treated with B7H6-siRNA and temozolomide, separately and in combination. Cell viability, stemness, cell migration, and apoptosis were measured. The results of this work presented the synergistic effect of B7H6-siRNA and temozolomide in inhibiting the cancerous features of the U87 cell line. Down-regulating B7H6-siRNA expression inhibited the cell viability of U87 glioblastoma cancer cells and increased their sensitivity to temozolomide. In addition, a not...
Source: Experimental Cell Research - May 29, 2023 Category: Cytology Authors: Nadia Allahyarzadeh Khiabani Mohammad Amin Doustvandi Fateme Mohammadnejad Elnaz Salmani Hassan Kohal Neda Boushehri Mahdi Jafarlou Behzad Baradaran Source Type: research

Naringenin Produces Neuroprotection Against LPS-Induced Dopamine Neurotoxicity via the Inhibition of Microglial NLRP3 Inflammasome Activation
Conclusions: This study demonstrated that NAR targeted microglial NLRP3 inflammasome to protect DA neurons against LPS-induced neurotoxicity. These findings suggest NAR might hold a promising therapeutic potential for PD. Background Parkinson's disease (PD) is the second most prevalent central nervous system (CNS) degenerative disease. It is characterized by slow and progressive loss of dopamine (DA) neurons in the midbrain substantia nigra (SN) with the accumulation of α-synuclein in Lewy bodies and neuritis (1). Although the etiology of PD remains unclear, amounts of studies have suggested that ne...
Source: Frontiers in Immunology - April 30, 2019 Category: Allergy & Immunology Source Type: research

An optimized ionizable cationic lipid for brain tumor-targeted siRNA delivery and glioblastoma immunotherapy
Biomaterials. 2022 Jun 22;287:121645. doi: 10.1016/j.biomaterials.2022.121645. Online ahead of print.ABSTRACTGlioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor with a high mortality rate. Immunotherapy has achieved promising clinical results in multiple cancers, but shows unsatisfactory outcome in GBM patients, and poor drug delivery across the blood-brain barrier (BBB) is believed to be one of the main limitations that hinder the therapeutic efficacy of drugs. Herein, a new cationic lipid nanoparticle (LNP) that can efficiently deliver siRNA across BBB and target mouse brain is prepared fo...
Source: Biomaterials - July 2, 2022 Category: Materials Science Authors: Shuhan Liu Ji Liu Haisong Li Kuirong Mao Haorui Wang Xiandi Meng Jialiang Wang Chenxi Wu Hongmei Chen Xin Wang Xiuxiu Cong Yue Hou Ye Wang Ming Wang Yong-Guang Yang Tianmeng Sun Source Type: research

Brain tumor-targeted therapy by systemic delivery of siRNA with Transferrin receptor-mediated core-shell nanoparticles
This study aims to investigate the therapeutic effects of intravenous administration of T7 peptide modified core-shell nanoparticles (named T7-LPC/siRNA NPs) on brain tumors. Layer-by-layer assembling of protamine/chondroitin sulfate/siRNA/cationic liposomes followed by T7 peptide modification has been carried out in order to obtain a targeted siRNA delivery system. In vitro cellular uptake experiments demonstrated a higher intracellular fluorescence intensity of siRNA in brain microvascular endothelial cells (BMVECs) and U87 glioma cells when treated with T7-LPC/siRNA NPs compared with PEG-LPC/siRNA NPs. In the co-culture...
Source: International Journal of Pharmaceutics - July 14, 2016 Category: Drugs & Pharmacology Source Type: research

Antiproliferative activity of CD44 siRNA-PEI-PEG nanoparticles in glioblastoma: involvement of AKT signaling
CONCLUSION AND IMPLICATIONS: Our results suggest that PEI-PEG-loaded CD44 siRNA may attenuate the cell cycle by suppressing AKT signaling pathway.PMID:34909046 | PMC:PMC8621842 | DOI:10.4103/1735-5362.329928
Source: Cell Research - December 15, 2021 Category: Cytology Authors: Parvaneh Mahinfar Ahad Mokhtarzadeh Behzad Baradaran Elham Siasi Torbati Source Type: research

Genetic Regulation of Liver Metabolites and Transcripts Linking to Biochemical-Clinical Parameters
Conclusion In summary, this study is the first to combine metabolomics, transcriptomics, and genome-wide association studies in a porcine model. Our results improve understanding of the genetic regulation of metabolites which link to transcripts and finally biochemical-clinical parameters. Further, high-performance profiling of metabolites as intermediate phenotypes is a potentially powerful approach to uncover how genetic variation affects metabolic and health status. Our results advance knowledge in areas of biomedical and agricultural interest and identify potential correlates of biomarkers, SNPs-metabolites, SNPs-tran...
Source: Frontiers in Genetics - April 16, 2019 Category: Genetics & Stem Cells Source Type: research

Enhanced nose-to-brain delivery of siRNA using hyaluronan-enveloped nanomicelles for glioma therapy
In conclusion, HA/DP7-C is a potential intranasal delivery system for siRNAs in glioma therapy.PMID:34973309 | DOI:10.1016/j.jconrel.2021.12.034
Source: Cancer Control - January 1, 2022 Category: Cancer & Oncology Authors: YuLing Yang XueYan Zhang SiWen Wu Rui Zhang BaiLing Zhou XiaoYu Zhang Lin Tang Yaomei Tian Ke Men Li Yang Source Type: research

siRNA as a tool to improve the treatment of brain diseases: Mechanism, targets and delivery.
Abstract As the population ages, brain pathologies such as neurodegenerative diseases and brain cancer increase their incidence, being the need to find successful treatments of upmost importance. Drug delivery to the central nervous system (CNS) is required in order to reach diseases causes and treat them. However, biological barriers, mainly blood-brain barrier (BBB), are the key obstacles that prevent the effectiveness of possible treatments due to their ability to strongly limit the perfusion of compounds into the brain. Over the past decades, new approaches towards overcoming BBB and its efflux transporters ha...
Source: Ageing Research Reviews - March 18, 2015 Category: Genetics & Stem Cells Authors: Gomes MJ, Martins S, Sarmento B Tags: Ageing Res Rev Source Type: research