scholarly journals Cardiac-targeted delivery of regulatory RNA molecules and genes for the treatment of heart failure

2010 ◽  
Vol 86 (3) ◽  
pp. 353-364 ◽  
Author(s):  
W. Poller ◽  
R. Hajjar ◽  
H. P. Schultheiss ◽  
H. Fechner
Keyword(s):  
Heart Failure ◽  
Targeted Delivery ◽  
Regulatory Rna ◽  
Rna Molecules

scholarly journals MicroRNAs in central nervous system disorders: current advances in pathogenesis and treatment

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Mona Hussein ◽  
Rehab Magdy
Keyword(s):  
Neurological Disorders ◽  
Target Genes ◽  
Transcriptional Regulators ◽  
Therapeutic Strategies ◽  
Regulatory Rna ◽  
Altered Expression ◽  
Rna Molecules ◽  
Central Nervous System Disorders ◽  
Novel Targets ◽  
Lateral Sclerosis

AbstractMicroRNAs (miRNAs) are a class of short, non-coding, regulatory RNA molecules that function as post transcriptional regulators of gene expression. Altered expression of multiple miRNAs was found to be extensively involved in the pathogenesis of different neurological disorders including Alzheimer’s disease, Parkinson’s disease, stroke, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington’s disease. miRNAs are implicated in the pathogenesis of excitotoxicity, apoptosis, oxidative stress, inflammation, neurogenesis, angiogenesis, and blood–brain barrier protection. Consequently, miRNAs can serve as biomarkers for different neurological disorders. In recent years, advances in the miRNA field led to identification of potentially novel prospects in the development of new therapies for incurable CNS disorders. MiRNA-based therapeutics include miRNA mimics and inhibitors that can decrease or increase the expression of target genes. Better understanding of the mechanisms by which miRNAs are implicated in the pathogenesis of neurological disorders may provide novel targets to researchers for innovative therapeutic strategies.

Bioinformatics Methods for Studying MicroRNA and ARE-Mediated Regulation of Post-Transcriptional Gene Expression

2010 ◽  
Vol 1 (3) ◽  
pp. 97-112 ◽  
Author(s):  
Richipal Singh Bindra ◽  
Jason T. L. Wang ◽  
Paramjeet Singh Bagga
Keyword(s):  
Mirna Target ◽  
Target Prediction ◽  
Untranslated Regions ◽  
Regulatory Rna ◽  
Rna Motifs ◽  
Protein Coding ◽  
Rna Molecules ◽  
Cellular Processes ◽  
Target Sites ◽  
Transcriptional Gene Regulation

MicroRNAs (miRNAs) are short single-stranded RNA molecules with 21-22 nucleotides known to regulate post-transcriptional expression of protein-coding genes involved in most of the cellular processes. Prediction of miRNA targets is a challenging bioinformatics problem. AU-rich elements (AREs) are regulatory RNA motifs found in the 3’ untranslated regions (UTRs) of mRNAs, and they play dominant roles in the regulated decay of short-lived human mRNAs via specific interactions with proteins. In this paper, the authors review several miRNA target prediction tools and data sources, as well as computational methods used for the prediction of AREs. The authors discuss the connection between miRNA and ARE-mediated post-transcriptional gene regulation. Finally, a data mining method for identifying the co-occurrences of miRNA target sites in ARE containing genes is presented.

scholarly journals Intracoronary delivery of recombinant TIMP-3 after myocardial infarction: effects on myocardial remodeling and function

2017 ◽  
Vol 313 (4) ◽  
pp. H690-H699 ◽  
Author(s):  
Shayne C. Barlow ◽  
Heather Doviak ◽  
Julia Jacobs ◽  
Lisa A. Freeburg ◽  
Paige E. Perreault ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Matrix Metalloproteinase ◽  
Reperfusion Injury ◽  
Targeted Delivery ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Myocardial Remodeling ◽  
Myocardial Ischemia And Reperfusion ◽  
End Diastolic Volume

Ischemia-reperfusion (IR) and myocardial infarction (MI) cause adverse left ventricular (LV) remodeling and heart failure and are facilitated by an imbalance in matrix metalloproteinase (MMP) activation and the endogenous tissue inhibitors of metalloproteinase (TIMPs). We have identified that myocardial injections of recombinant TIMP-3 (rTIMP-3; human full length) can interrupt post-MI remodeling. However, whether and to what degree intracoronary delivery of rTIMP-3 post-IR is feasible and effective remained to be established. Pigs (25 kg) underwent coronary catheterization and balloon occlusion of the left anterior descending coronary artery (LAD) for 90 min whereby at the final 4 min, rTIMP-3 (30 mg, n = 9) or saline was infused in the distal LAD. LV echocardiography was performed at 3–28 days post-IR, and LV ejection fraction (EF) and LV end-diastolic volume were measured. LV EF fell and LV end-diastolic volume increased from baseline (pre-IR) values (66 ± 1% and 40 ± 1 ml, respectively, means ± standard deviation) in both groups; however, the extent of LV dilation was reduced in the rTIMP-3 group by 40% at 28 days post-IR ( P < 0.05) and the fall in LV EF was attenuated. Despite equivalent plasma troponin levels (14 ± 3 ng/ml), computed MI size at 28 days was reduced by over 45% in the rTIMP-3 group ( P < 0.05), indicating that rTIMP-3 treatment abrogated MI expansion post-IR. Plasma NH2-terminal pro-brain natriuretic peptide levels, an index of heart failure progression, were reduced by 25% in the rTIMP-3 group compared with MI saline values ( P < 0.05). Although the imbalance between MMPs and TIMPs has been recognized as a contributory factor for post-MI remodeling, therapeutic strategies targeting this imbalance have not been forthcoming. This study is the first to demonstrate that a relevant delivery approach (intracoronary) using rTIMP can alter the course of post-MI remodeling. NEW & NOTEWORTHY Myocardial ischemia and reperfusion injury remain significant causes of morbidity and mortality whereby alterations in the balance between matrix metalloproteinase and tissue inhibitor of metalloproteinase have been identified as contributory biological mechanisms. This novel translational study advances the concept of targeted delivery of recombinant proteins to modify adverse myocardial remodeling in ischemia-reperfusion injury.

scholarly journals A Versatile Method to Design Stem-Loop Primer-Based Quantitative PCR Assays for Detecting Small Regulatory RNA Molecules

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e55168 ◽  
Author(s):  
Zsolt Czimmerer ◽  
Julianna Hulvely ◽  
Zoltan Simandi ◽  
Eva Varallyay ◽  
Zoltan Havelda ◽  
...  
Keyword(s):  
Quantitative Pcr ◽  
Regulatory Rna ◽  
Stem Loop ◽  
Rna Molecules ◽  
Loop Primer ◽  
Small Regulatory Rna ◽  
Pcr Assays

scholarly journals Regulatory RNA molecules

2006 ◽  
Vol 27 (3) ◽  
pp. 124
Author(s):  
Stephen M Kwong ◽  
Neville Firth
Keyword(s):  
Gene Regulation ◽  
Antisense Rna ◽  
Current Knowledge ◽  
Regulatory Rna ◽  
Rna Molecules ◽  
Genetic Elements ◽  
Regulatory Systems ◽  
Regulatory Rnas

Numerous examples of antisense RNA-mediated gene regulation have been found in bacteria. Such regulatory systems were first identified on accessory genetic elements such as plasmids, transposons and phages, and it is from these that most of our current knowledge of regulatory RNAs is drawn.

scholarly journals Regulatory RNAs in Bacillus subtilis: a Gram-Positive Perspective on Bacterial RNA-Mediated Regulation of Gene Expression

2016 ◽  
Vol 80 (4) ◽  
pp. 1029-1057 ◽  
Author(s):  
Ruben A. T. Mars ◽  
Pierre Nicolas ◽  
Emma L. Denham ◽  
Jan Maarten van Dijl
Keyword(s):  
Gene Expression ◽  
Bacillus Subtilis ◽  
Regulation Of Gene Expression ◽  
Regulatory Rna ◽  
Gram Positive ◽  
Content Type ◽  
Rna Molecules ◽  
Small Regulatory Rnas ◽  
Regulatory Rnas ◽  
The Stability

SUMMARYBacteria can employ widely diverse RNA molecules to regulate their gene expression. Such molecules includetrans-acting small regulatory RNAs, antisense RNAs, and a variety of transcriptional attenuation mechanisms in the 5′ untranslated region. Thus far, most regulatory RNA research has focused on Gram-negative bacteria, such asEscherichia coliandSalmonella. Hence, there is uncertainty about whether the resulting insights can be extrapolated directly to other bacteria, such as the Gram-positive soil bacteriumBacillus subtilis. A recent study identified 1,583 putative regulatory RNAs inB. subtilis, whose expression was assessed across 104 conditions. Here, we review the current understanding of RNA-based regulation inB. subtilis, and we categorize the newly identified putative regulatory RNAs on the basis of their conservation in other bacilli and the stability of their predicted secondary structures. Our present evaluation of the publicly available data indicates that RNA-mediated gene regulation inB. subtilismostly involves elements at the 5′ ends of mRNA molecules. These can include 5′ secondary structure elements and metabolite-, tRNA-, or protein-binding sites. Importantly, sense-independent segments are identified as the most conserved and structured potential regulatory RNAs inB. subtilis. Altogether, the present survey provides many leads for the identification of new regulatory RNA functions inB. subtilis.

scholarly journals Optoribogenetic control of regulatory RNA molecules

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Sebastian Pilsl ◽  
Charles Morgan ◽  
Moujab Choukeife ◽  
Andreas Möglich ◽  
Günter Mayer
Keyword(s):  
Gene Expression ◽  
Protein Function ◽  
Mammalian Cells ◽  
Regulatory Rna ◽  
Rna Molecules ◽  
Cell State ◽  
Non Invasive ◽  
Micro Rnas ◽  
Short Hairpin ◽  
Regulatory Rnas

Abstract Short regulatory RNA molecules underpin gene expression and govern cellular state and physiology. To establish an alternative layer of control over these processes, we generated chimeric regulatory RNAs that interact reversibly and light-dependently with the light-oxygen-voltage photoreceptor PAL. By harnessing this interaction, the function of micro RNAs (miRs) and short hairpin (sh) RNAs in mammalian cells can be regulated in a spatiotemporally precise manner. The underlying strategy is generic and can be adapted to near-arbitrary target sequences. Owing to full genetic encodability, it establishes optoribogenetic control of cell state and physiology. The method stands to facilitate the non-invasive, reversible and spatiotemporally resolved study of regulatory RNAs and protein function in cellular and organismal environments.

scholarly journals Synthesis and characterization of peptide conjugated human serum albumin nanoparticles for targeted cardiac uptake and drug delivery

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0254305
Author(s):  
Nikita Lomis ◽  
Susan Westfall ◽  
Dominique Shum-Tim ◽  
Satya Prakash
Keyword(s):  
Heart Failure ◽  
Drug Delivery ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Targeted Delivery ◽  
H9c2 Cells ◽  
Albumin Nanoparticles ◽  
Body Retention

Congestive heart failure, a prominent cardiovascular disease results primarily from myocardial infarction or ischemia. Milrinone (MRN), a widely used clinical drug for heart failure, improves myocardial contractility and cardiac function through its inotropic and vasodilatory effects. However, lacking target specificity, it exhibits low bioavailability and lower body retention time. Therefore, in this study, angiotensin II (AT1) peptide conjugated human serum albumin nanoparticles (AT1-HSA-MRN-NPs) have been synthesized for targeted delivery of MRN to the myocardium, overexpressing AT1 receptors under heart failure. The NPs were surface functionalized through a covalent conjugation reaction between HSA and AT1. Nanoparticle size was 215.2±4.7 nm and zeta potential -28.8±2.7 mV and cumulative release of MRN was ~72% over 24 hrs. The intracellular uptake of nanoparticles and cell viability was studied in H9c2 cells treated with AT1-MRN-HSA-NPs vs the control non-targeted drug, MRN Lactate under normal, hypoxic and hypertrophic conditions. The uptake of AT1-HSA-MRN-NPs in H9c2 cells was significantly higher as compared to non-targeted nanoparticles, and the viability of H9c2 cells treated with AT1-MRN-HSA-NPs vs MRN Lactate was 73.4±1.4% vs 44.9±1.4%, respectively. Therefore, AT1-HSA-MRN-NPs are safe for in vivo use and exhibit superior targeting and drug delivery characteristics for treatment of heart failure.

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