PubMed Journals Articles About "Studies Impending Oligonucleotide Therapeutics Simulated Biofluids" RSS

03:59 EDT 26th March 2019 | BioPortfolio

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Showing "Studies Impending Oligonucleotide Therapeutics Simulated Biofluids" PubMed Articles 1–25 of 27,000+

Studies of Impending Oligonucleotide Therapeutics in Simulated Biofluids.

Synthetic oligonucleotides, their complexes and conjugates with other biomolecules represent valuable research tools and therapeutic agents. In spite of growing applications in basic research and clinical science, only few studies have addressed the issue of such compounds' stability in biological media. Herein, we studied the stability of two therapeutically relevant oligonucleotide probes in simulated biofluids; the 21 nucleotide-long DNA/locked nucleic acid oligonucleotide ON targeted toward cancer-assoc...

Development of a detection method for antisense oligonucleotides in mouse kidneys by MALDI imaging mass spectrometry.

Oligonucleotide therapeutics have been recently gaining more attention, but its pharmacokinetic evaluation methods are still not sufficient, and in particular, more tools are needed to evaluate their tissue distribution and metabolites. We developed a matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) based method to evaluate the tissue distribution of oligonucleotide therapeutics.

Large Differences in Small RNA Composition Between Human Biofluids.

Extracellular microRNAs (miRNAs) and other small RNAs are implicated in cellular communication and may be useful as disease biomarkers. We systematically compared small RNAs in 12 human biofluid types using RNA sequencing (RNA-seq). miRNAs and tRNA-derived RNAs (tDRs) accounted for the majority of mapped reads in all biofluids, but the ratio of miRNA to tDR reads varied from 72 in plasma to 0.004 in bile. miRNA levels were highly correlated across all biofluids, but levels of some miRNAs differed markedly b...

Synthesis and Application of Interstrand Cross-Linked Duplexes by Covalently Linking a Pair of Abasic Sites.

Interstrand cross-linking of DNA or RNA inhibits the double strands from dissociating into single strands. This article contains detailed procedures for the synthesis of a novel interstrand cross-linker that comprises a bis-aminooxy naphthalene derivative and a description of its use in the preparation of sequence-specific interstrand cross-linked oligonucleotide duplexes. The interstrand cross-linker covalently connects a pair of apurinic/apyrimidinic sites in DNA/RNA duplexes with bis(aminooxy) groups. Th...


Vibrational spectroscopy techniques such as Raman and IR (infrared) allow real-time, non-invasive and non-destructiveanalysis of organic compounds with good limit-of-detection. This study aims to show the progress of clinical diagnosis and prognosis due to advances of vibrational spectroscopy techniques in biofluids through extensive literature review. This review was performed by searching for studies using the keywords "biofluids or biological fluids" and "diagnostic techniques" in PubMed, Scopus and Goog...

The use of fast photochemical oxidation of proteins coupled with mass spectrometry in protein therapeutics discovery and development.

Structural analysis of protein therapeutics is a challenging task owing to complexities associated with large molecular size and 3D structures. Recent advances in fast photochemical oxidation of proteins (FPOP) coupled with mass spectrometry (MS) have provided a means to characterize higher order structure (HOS) of protein therapeutics in solution. In this review, the utility of FPOP-MS in protein therapeutics discovery and development is presented, focusing on the principles and applications of epitope map...

Application of Physiologically-Based Pharmacokinetic Modeling to Predict Pharmacokinetics in Healthy Japanese Subjects.

Pharmacokinetics (PK) in Japanese healthy subjects were simulated for nine compounds using physiologically based pharmacokinetic (PBPK) models parameterized with physicochemical properties, preclinical absorption, distribution, metabolism, and excretion (ADME) data, and clinical PK data from non-Japanese subjects. For each dosing regimen, 100 virtual trials were simulated and predicted/observed ratios for C and AUC were calculated. As qualification criteria, it was pre-specified that over 80% of simulated t...

Rabbit models of human diseases for diagnostics and therapeutics development.

This review presents some examples of studies using the European rabbit (Oryctolagus cuniculus) that have led to, and continue to, contribute to advancement of understanding of human diseases as well as therapeutics development. In addition, we tabulate FDA-approved rabbit polyclonal and rabbit monoclonal antibodies (mAbs) that are used for diagnostic applications, as well as an overview of some "humanized" or otherwise altered rabbit mAbs that are in initial phase I, II, or advanced to phase III clinical t...

Oligonucleotide-modulated photocurrent enhancement of a tetracationic porphyrin for label-free homogeneous photoelectrochemical biosensing.

This work reports the first demonstration of an oligonucleotide-modulated label-free homogeneous photoelectrochemical (PEC) biosensing platform based on the adsorption of tetracationic porphyrin (denoted as TMPyP here) onto 1-naphthalenesulfonate anion (NS)-grafted indium tin oxide electrode (denoted as TMPyP-NS-ITO), which generates a stable and rapid photocurrent response. We found that when NS-ITO electrode was subjected to single-stranded oligonucleotide (ssON) before TMPyP adsorption, a remarkable enha...

Retroperitoneal Liposarcoma Masquerading As An Impending Rupture of Inflammatory Abdominal Aortic Aneurysm.

We present a unique case scenario of a periaortic liposarcoma masquerading as an impending rupture of an inflammatory abdominal aortic aneurysm (AAA).

Impending Paradoxical Embolism.

Impending paradoxical embolism (IPDE) is the presence of a thrombus in the patent foramen ovale (PFO). Usually, IPDE is diagnosed by echocardiography or an Multislice computer tomography (MSCT) scan and is performed during the evaluation of a patient presenting with suspected pulmonary embolism (PE). We report two patients who presented with IPDE and were successfully treated with cardiac surgery and thrombolytic therapy. Thus, we focus our discussion on the diagnosis and treatment modalities of this rare e...

Splice-Modulating Oligonucleotide QR-110 Restores CEP290 mRNA and Function in Human c.2991+1655A>G LCA10 Models.

Leber congenital amaurosis type 10 (LCA10) is a severe inherited retinal dystrophy associated with mutations in CEP290. The deep intronic c.2991+1655A>G mutation in CEP290 is the most common mutation in LCA10 individuals and represents an ideal target for oligonucleotide therapeutics. Here, a panel of antisense oligonucleotides was designed to correct the splicing defect associated with the mutation and screened for efficacy and safety. This identified QR-110 as the best-performing molecule. QR-110 restore...

The Assembly of Fluorescently Labeled Peptide-Oligonucleotide Conjugates via Orthogonal Ligation Strategies.

Efficient intracellular delivery is critical to the successful application of synthetic antisense oligonucleotides (ASOs) to modulate gene expression. The conjugation of cell-penetrating peptides (CPPs) to ASOs has been shown to significantly improve their intracellular delivery. It is important, however, that formation of the covalent linkage between the peptide and oligonucleotide is efficient and orthogonal, to ensure high yields and a homogeneous product. Described herein are efficient and facile method...

Tumour size can have an impact on the outcomes of epidemiological studies on second cancers after radiotherapy.

Obtaining a correct dose-response relationship for radiation-induced cancer after radiotherapy presents a major challenge for epidemiological studies. The purpose of this paper is to gain a better understanding of the associated uncertainties. To accomplish this goal, some aspects of an epidemiological study on breast cancer following radiotherapy of Hodgkin's disease were simulated with Monte Carlo methods. It is demonstrated that although the doses to the breast volume are calculated by one treatment plan...

Feasibility and Safety of Multicenter Tissue and Biofluid Sampling for α-Synuclein in Parkinson's Disease: The Systemic Synuclein Sampling Study (S4).

α-synuclein is a lead Parkinson's disease (PD) biomarker. There are conflicting reports regarding accuracy of α-synuclein in different tissues and biofluids as a PD biomarker, and the within-subject anatomical distribution of α-synuclein is not well described. The Systemic Synuclein Sampling Study (S4) aims to address these gaps in knowledge. The S4 is a multicenter, cross-sectional, observational study evaluating α-synuclein in multiple tissues and biofluids in PD and healthy controls (HC).

Multiplex Single-Molecule DNA Barcoding Using an Oligonucleotide Ligation Assay.

Detection of specific nucleic acid sequences is invaluable in biological studies such as genetic disease diagnostics and genome profiling. Here, we developed a highly sensitive and specific detection method that combines an advanced oligonucleotide ligation assay with multicolor single-molecule fluorescence. We demonstrated that under our experimental conditions, 7-nucleotide long DNA barcodes have the optimal short length to ascertain specificity while being long enough for sufficient ligation. Using four ...

The effects of computer-based simulations on speech-language pathology student performance.

The purpose of this study was to assess the efficacy of a computer-based simulated learning environment on student learning in speech-language pathology. Despite a growing trend in the implementation of computer-based simulated learning environments, no research yet supports its efficacy. In addition, although over half of the United States' speech-language pathologists work in school systems, no studies have investigated simulated learning environments that focus on pediatric developmental language disorde...

NS-065/NCNP-01: An Antisense Oligonucleotide for Potential Treatment of Exon 53 Skipping in Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD), the most common lethal heritable childhood disease, is caused by mutations in the DMD gene that result in the absence of functional dystrophin protein. Exon skipping mediated by antisense oligonucleotides has recently emerged as an effective approach for the restoration of dystrophin, and skipping of exon 51 of DMD has received accelerated approval. Identifying antisense sequences that can provide the highest possible skipping efficiency is crucial for future clinical appl...

Serum amyloid a as an indicator of impending xenograft failure: Experimental studies.

There is well-documented systemic inflammatory response in xenograft recipients to the presence of a pig graft. Serum amyloid A (SAA) is an inflammatory marker that is elevated in various pathological states. The assay used to measure it is (i) simple, (ii) relatively inexpensive, and (iii) provides an answer within minutes.

DNA Strand Buffers.

A buffer reaction actively resists changes to the concentration of a chemical species. Typically, buffering reactions have only been able to regulate the concentration of hydronium (i.e., pH) and other ions. Here, we develop a new class of buffers that regulate the concentrations of short sequences of DNA (i.e., oligonucleotides). A buffer's behavior is determined by its set point concentration, capacity to resist disturbances, and response time after a disturbance. We provide simple mathematical formulas f...

Antisense Oligonucleotides Targeting Angiogenic Factors as Potential Cancer Therapeutics.

Cancer is one of the leading causes of death worldwide, and conventional cancer therapies such as surgery, chemotherapy, and radiotherapy do not address the underlying molecular pathologies, leading to inadequate treatment and tumor recurrence. Angiogenic factors, such as EGF, PDGF, bFGF, TGF-β, TGF-α, VEGF, endoglin, and angiopoietins, play important roles in regulating tumor development and metastasis, and they serve as potential targets for developing cancer therapeutics. Nucleic acid-based therapeutic...

Effects of miR-503-5p on apoptosis of human pulmonary microvascular endothelial cells in simulated microgravity.

Recent studies have shown that microRNA (miRNAs) can play important roles in the regulation of endothelial cell (EC) function. However, the expression profile of miRNAs and their effects on the apoptosis of ECs under microgravity conditions remains unclear. In this study, the apoptosis of human pulmonary microvascular endothelial cells (HPMECs) under simulated microgravity was identified by Annexin V and propidium iodide double staining and transmission electron microscopy. miRNA microarray assay was used t...

Statins and risk of cataracts: a systematic review and meta-analysis of observational studies.

Two previous meta-analyses evaluated the risk of cataracts associated with statins, but did not include relevant studies suggesting a cataratogenic effect.

Heparin-binding EGF-like growth factor (HB-EGF) antisense oligonucleotide protected against hyperlipidemia-associated atherosclerosis.

Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model.

Letter: proton pump inhibitors use and risk of hepatocellular carcinoma: A meta-analysis of observational studies.

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