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https://www.readbyqxmd.com/read/28918049/silencing-vdac1-expression-by-sirna-inhibits-cancer-cell-proliferation-and-tumor-growth-in%C3%A2-vivo
#1
Tasleem Arif, Lilia Vasilkovsky, Yael Refaely, Alexander Konson, Varda Shoshan-Barmatz
No abstract text is available yet for this article.
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918036/therapeutic-suppression-of-mir-4261-attenuates-colorectal-cancer-by-targeting-mcc
#2
Guanming Jiao, Qi Huang, Muren Hu, Xuchun Liang, Fuchen Li, Chunling Lan, Wencheng Fu, Yu An, Bin Xu, Jinzhe Zhou, Junjie Xiao
The mutated in colorectal cancer (MCC) gene is an important colorectal tumor suppressor gene, although few studies have reported the microRNA(s) that could directly target MCC in colorectal cancer. Here, we used microRNA (miRNA) target prediction algorithms, and previously reported microarray data in human colorectal cancer found that only miR-4261 was predicted by all three databases to directly target MCC. Based on specimens from our own cohort of colorectal cancer patients, we further demonstrated that miR-4261 was overexpressed in colorectal cancer...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918034/a-simple-and-cost-effective-approach-for-in%C3%A2-vitro-production-of-sliced-sirnas-as-potent-triggers-for-rnai
#3
Guihua Sun, Arthur D Riggs
We have studied the molecular properties of in-vitro-transcribed sliced small interfering RNAs (tsli-siRNAs) as an alternative RNAi agent for chemically synthesized siRNA. We describe here a simple and cost-effective procedure for high-purity production of tsli-siRNA using bacteriophage T7 RNA polymerases. tsli-siRNAs exhibit potent gene knockdown effects, with efficacy comparable with that of chemically synthesized sli-siRNAs and classical siRNAs. Furthermore, we found that it is very easy to prepare potent tsli-siRNAs with modified bases, such as 2'-fluorine- or biotin-16-modified tsli-siRNAs...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918033/six-highly-conserved-targets-of-rnai-revealed-in-hiv-1-infected-patients-from-russia-are-also-present-in-many-hiv-1-strains-worldwide
#4
Olga V Kretova, Daria M Fedoseeva, Maria A Gorbacheva, Natalya M Gashnikova, Maria P Gashnikova, Nataliya V Melnikova, Vladimir R Chechetkin, Yuri V Kravatsky, Nickolai A Tchurikov
RNAi has been suggested for use in gene therapy of HIV/AIDS, but the main problem is that HIV-1 is highly variable and could escape attack from the small interfering RNAs (siRNAs) due to even single nucleotide substitutions in the potential targets. To exhaustively check the variability in selected RNA targets of HIV-1, we used ultra-deep sequencing of six regions of HIV-1 from the plasma of two independent cohorts of patients from Russia. Six RNAi targets were found that are invariable in 82%-97% of viruses in both cohorts and are located inside the domains specifying reverse transcriptase (RT), integrase, vpu, gp120, and p17...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918028/human-dmbt1-derived-cell-penetrating-peptides-for-intracellular-sirna-delivery
#5
Martina Tuttolomondo, Cinzia Casella, Pernille Lund Hansen, Ester Polo, Luciana M Herda, Kenneth A Dawson, Henrik J Ditzel, Jan Mollenhauer
Small interfering RNA (siRNA) is a promising molecule for gene therapy, but its therapeutic administration remains problematic. Among the recently proposed vectors, cell-penetrating peptides show great promise in in vivo trials for siRNA delivery. Human protein DMBT1 (deleted in malignant brain tumor 1) is a pattern recognition molecule that interacts with polyanions and recognizes and aggregates bacteria. Taking advantage of these properties, we investigated whether specific synthetic DMBT1-derived peptides could be used to formulate nanoparticles for siRNA administration...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918019/dual-tumor-targeting-nanocarrier-system-for-sirna-delivery-based-on-prna-and-modified-chitosan
#6
Lin Li, Xiaoqin Hu, Min Zhang, Siyu Ma, Fanglin Yu, Shiqing Zhao, Nan Liu, Zhiyuan Wang, Yu Wang, Hua Guan, Xiujie Pan, Yue Gao, Yue Zhang, Yan Liu, Yang Yang, Xuemei Tang, Mingyuan Li, Cheng Liu, Zhiping Li, Xingguo Mei
Highly specific and efficient delivery of siRNA is still unsatisfactory. Herein, a dual tumor-targeting siRNA delivery system combining pRNA dimers with chitosan nanoparticles (CNPPs) was designed to improve the specificity and efficiency of siRNA delivery. In this dual delivery system, folate-conjugated and PEGylated chitosan nanoparticles encapsulating pRNA dimers were used as the first class of delivery system and would selectively deliver intact pRNA dimers near or into target cells. pRNA dimers simultaneously carrying siRNA and targeting aptamer, the second class of delivery system, would specifically deliver siRNA into the target cells via aptamer-mediated endocytosis or proper particle size...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918018/locked-nucleic-acid-gapmers-and-conjugates-potently-silence-adam33-an-asthma-associated-metalloprotease-with-nuclear-localized-mrna
#7
Hannah M Pendergraff, Pranathi Meda Krishnamurthy, Alexandre J Debacker, Michael P Moazami, Vivek K Sharma, Liisa Niitsoo, Yong Yu, Yen Nee Tan, Hans Michael Haitchi, Jonathan K Watts
Two mechanisms dominate the clinical pipeline for oligonucleotide-based gene silencing, namely, the antisense approach that recruits RNase H to cleave target RNA and the RNAi approach that recruits the RISC complex to cleave target RNA. Multiple chemical designs can be used to elicit each pathway. We compare the silencing of the asthma susceptibility gene ADAM33 in MRC-5 lung fibroblasts using four classes of gene silencing agents, two that use each mechanism: traditional duplex small interfering RNAs (siRNAs), single-stranded small interfering RNAs (ss-siRNAs), locked nucleic acid (LNA) gapmer antisense oligonucleotides (ASOs), and novel hexadecyloxypropyl conjugates of the ASOs...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918016/therapeutic-mirna-and-sirna-moving-from-bench-to-clinic-as-next-generation-medicine
#8
REVIEW
Chiranjib Chakraborty, Ashish Ranjan Sharma, Garima Sharma, C George Priya Doss, Sang-Soo Lee
In the past few years, therapeutic microRNA (miRNA) and small interfering RNA (siRNA) are some of the most important biopharmaceuticals that are in commercial space as future medicines. This review summarizes the patents of miRNA- and siRNA-based new drugs, and also provides a snapshot about significant biopharmaceutical companies that are investing for the therapeutic development of miRNA and siRNA molecules. An insightful view about individual siRNA and miRNA drugs has been depicted with their present status, which is gaining attention in the therapeutic landscape...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917924/synthesis-of-amphoteric-curdlan-derivatives-for-delivery-of-therapeutic-nucleic-acids
#9
Yao Tong, Tsogzolmaa Ganbold, Huricha Baigude
Cationic polymers are powerful carriers for intracellular delivery of therapeutic nucleic acids. However, the positively charged macromolecules have considerable cytotoxicity and often induce irreversible damages to the cells and tissues, which greatly negate the clinical application of such materials as drug delivery system. Herein, we report the synthesis of novel amphoteric polymers based on curdlan, and the evaluation of their cytotoxicity as well as the nucleic acid delivery efficiency. β-(1,3)-polyglucuronic acid, a TEMPO-oxidized derivative of curdlan, was chemically modified by conjugation of tetraethylenepentamine...
November 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28917843/rapgef2-a-guanine-nucleotide-exchange-factor-for-rap1-small-gtpases-plays-a-crucial-role-in-adherence-junction-aj-formation-in-radial-glial-cells-through-erk-mediated-upregulation-of-the-aj-constituent-protein-expression
#10
Maged Ibrahim Farag, Yoko Yoshikawa, Kazuhiro Maeta, Tohru Kataoka
Rapgef2 and Rapgef6 define a subfamily of guanine nucleotide exchange factors for Rap1, characterized by possession of the Ras/Rap-associating domains and implicated in the etiology of schizophrenia. We previously found that dorsal telencephalon-specific Rapgef2 conditional knockout mice exhibits severe defects in formation of apical surface adherence junctions (AJs) and localization of radial glial cells (RGCs). In this study, we analyze the underlying molecular mechanism by using primary cultures of RGCs established from the developing cerebral cortex...
September 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28916723/fibroblast-growth-factor-2-fgf2-regulates-cytoglobin-expression-and-activation-of-human-hepatic-stellate-cells-via-jnk-signaling
#11
Misako Sato-Matsubara, Tsutomu Matsubara, Atsuko Daikoku, Yoshinori Okina, Lisa Longato, Krista Rombouts, Le Thi Thanh Thuy, Jun Adachi, Takeshi Tomonaga, Kazuo Ikeda, Katsutoshi Yoshizato, Massimo Pinzani, Norifumi Kawada
Cytoglobin (CYGB) belongs to the mammalian globin family and is exclusively expressed in hepatic stellate cells (HSCs) in the liver. In addition to its gas-binding ability, CYGB is relevant to hepatic inflammation, fibrosis, and cancer because of its antioxidative properties; however, the regulation of CYGB gene expression remains unknown. Here, we sought to identify factors that induce CYGB expression in HSCs and to clarify the molecular mechanism involved. We used the human HSC cell line HHSteC and primary human HSCs isolated from intact human liver tissues...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916481/identification-of-2-4-dihydroxy-5-pyrimidinyl-imidothiocarbomate-as-a-novel-inhibitor-to-y-box-binding-protein-1-yb-1-and-its-therapeutic-actions-against-breast-cancer
#12
Vinoth Prasanna Gunasekaran, Kumari Nishi, Dakshinamurthy Sivakumar, Thirunavukkarasu Sivaraman, Ganeshan Mathan
In spite of advances in breast cancer treatment and early diagnosis, drug toxicity, cancer relapse, multidrug resistance and metastasis are the major impediment to the developments of efficient drugs. However, unique druggable targets of cancer cells distinct from the normal cells provide new rationale in cancer treatment. Previous reports clearly emphasize the differential expression and localization of Y box binding protein-1 (YB-1) between normal breast tissues and different stages of breast cancer. Y box binding protein-1 is DNA as well as RNA binding protein involved in transcription and translation regulation of various proteins involved in cancer progression, apoptosis, cell cycle, epithelial to mesenchymal transition (EMT) and drug resistance...
September 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28916474/nox4-regulates-the-enos-uncoupling-process-in-aging-endothelial-cells
#13
Hwa-Young Lee, Hyung-Ryong Kim, Han-Jung Chae
ROS and its associated signaling contribute to vascular aging-associated endothelial disturbance. Since the non-effective endothelial nitric oxide synthase (eNOS) coupling status is related to vascular aging-related phenotypes, eNOS coupled/uncoupled system signaling was studied in human umbilical vein endothelial cells (HUVEC). Nitric oxide (NO) and eNOS Ser1177 were significantly decreased, whereas O2(-) (superoxide anion radical) increased with passage number. In aging cells, NADPH oxidase 4 (Nox4), one of the main superoxide generating enzymes, and its associated protein disulfide isomerase (PDI) chaperone were highly activated, and the resultant ER redox imbalance leads to disturbance of protein folding capability, namely endoplasmic reticulum (ER) stress, ultimately inducing dissociation between HSP90 and IRE-1α or PERK, decreasing HSP90 stability and dissociating the binding of eNOS from the HSP90 and leading to eNOS uncoupling...
September 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28916296/folate-targeted-amphiphilic-cyclodextrin-nanoparticles-incorporating-a-fusogenic-peptide-deliver-therapeutic-sirna-and-inhibit-the-invasive-capacity-of-3d-prostate-cancer-tumours
#14
James C Evans, Meenakshi Malhotra, Katrina Sweeney, Raphael Darcy, Colleen C Nelson, Brett G Hollier, Caitriona M O'Driscoll
The main barrier to the development of an effective RNA interference (RNAi) therapy is the lack of a suitable delivery vector. Modified cyclodextrins have emerged in recent years for the delivery of siRNA. In the present study, a folate-targeted amphiphilic cyclodextrin was formulated using DSPE-PEG5000-folate to target prostate cancer cells. The fusogenic peptide GALA was included in the formulation to aid in the endosomal release of siRNA. Targeted nanoparticles were less than 200nm in size with a neutral surface charge...
September 12, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28916266/grass-carp-ctenopharyngodon-idella-stat3-regulates-the-eif2%C3%AE-phosphorylation-through-interaction-with-pkr
#15
Liqiang Wang, Zhen Wu, Qingli Huang, Keyi Huang, Guoqin Qi, Chuxin Wu, Huiling Mao, Xiaowen Xu, Haizhou Wang, Chengyu Hu
In mammals, STAT3 (Signal transducer and activator of transcription 3) plays an important role in growth, multiplication, differentiation and participates in inflammation, tumorigenesis, metabolic disorders and immune response. STAT3 is a protein that shuttles between the nucleus and cytoplasm. Compared to the STAT3 in cell nucleus, we did not know the function of STAT3 in cytoplasm for a long time. Some recent studies have shown that cytoplasmic STAT3 regulates autophagy through the interaction with the double-stranded RNA-activated protein kinase (PKR), which plays an important role in cellular antiviral response...
September 12, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28915597/il-8-promotes-inflammatory-mediators-and-stimulates-activation-of-p38-mapk-erk-nf-%C3%AE%C2%BAb-pathway-and-reduction-of-jnk-in-hnscc
#16
Leong-Perng Chan, Cheng Liu, Feng-Yu Chiang, Ling-Feng Wang, Ka-Wo Lee, Wan-Ting Chen, Po-Lin Kuo, Chia-Hua Liang
This investigation identifies interleukin 8 (IL-8) as the main inflammatory mediator in head and neck squamous cell carcinoma (HNSCC). The expressions of chemokines of IL-8, IL-1β and IL-6 and the cytokines of tumor necrosis factor-α (TNF-α) were higher in HNSCC patient tissues than in non-cancerous matched tissues (NCMT) whereas the expression of IL-10 was lower. IL-8 is most highly expressed in the tissues of patients with HNSCC. Treatment of HNSCC cells with IL-8 increased the secretion of IL-1β, IL-6 and TNF-α and reduced IL-10 expression; the increase in the expression of IL-1β was particularly considerable...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914970/microrna-410-is-involved-in-mitophagy-after-cardiac-ischemia-reperfusion-injury-by-targeting-high-mobility-group-box-1-protein
#17
Fan Yang, Tong Li, Zhihuan Dong, Rui Mi
Mitochondrial dysfunction has emerged as a critical pathophysiological factor of myocardial ischemia/reperfusion (I/R) injury. A thorough understanding of mitochondrial dysfunction during I/R at the molecular level is urgently needed. One prominent microRNA, miR-410, was previously reported to be dynamically regulated in diverse cardiomyopathies, but its mechanism is unclear. In the present study, in a cardiac I/R injury mice model, the expression of miR-410 was significantly upregulated, accompanied with decreased mitochondrial function and mitophagy deficit...
September 15, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28914550/socs3-participates-in-cholinergic-pathway-regulation-of-synovitis-in-rheumatoid-arthritis
#18
Tong Li, Shiyao Wu, Sha Li, Xuelian Bai, Hui Luo, Xiaoxia Zuo
Stimulation of the cholinergic inflammatory pathway can promote collagen-induced arthritis (CIA) and inhibit synovitis by Janus kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 signaling. Suppressor of cytokine signaling (SOCS) protein can also regulate inflammatory processes and activate JAK/STAT signal transduction, but its involvement in rheumatoid arthritis (RA) has not been demonstrated. This study investigated the effect of SOCS on cholinergic pathway regulation of synovitis in the fibroblast-like synoviocytes (FLSs) of RA and CIA mice...
September 15, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28914370/thioredoxin-1-is-associated-with-the-proliferation-and-apoptosis-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#19
Tianbao Lu, Ming Zong, Shasha Fan, Ying Lu, Shanhan Yu, Lieying Fan
We aimed to investigate the possible effects of thioredoxin 1 (Trx1) on the proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) and elucidate the possible mechanisms involved. We investigated the distribution and expression of Trx1 in synovial tissues from RA and osteoarthritis (OA) patients by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) analyses. RA-FLSs were isolated and cultured under normoxic (21% oxygen) or hypoxic (3% oxygen) concentrations...
September 15, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28913715/oxidized-low-density-lipoprotein-oxldl-affects-load-free-cell-shortening-of-cardiomyocytes-in-a-proprotein-convertase-subtilisin-kexin-9-pcsk9-dependent-way
#20
Klaus-Dieter Schlüter, Annemarie Wolf, Martin Weber, Rolf Schreckenberg, Rainer Schulz
Recent studies have documented that oxidized low-density lipoprotein cholesterol (oxLDL) levels directly impact myocardial structure and function. However, the molecular mechanisms by which oxLDL affects cardiac myocytes are not well established. We addressed the question whether oxLDL modifies load-free cell shortening, a standardized readout of cardiac cellular function, and investigated whether proprotein convertase subtilisin/kexin-9 (PCSK9) is involved on oxLDL-dependent processes. Adult rat ventricular cardiomyocytes were isolated and incubated for 24 h with oxLDL...
September 14, 2017: Basic Research in Cardiology
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