Widespread 8-oxoguanine modifications of miRNA seeds differentially regulate redox-dependent cancer development.

Oxidative stress contributes to tumourigenesis by altering gene expression. One accompanying modification, 8-oxoguanine (oG) can change RNA-RNA interactions via oG•A base pairing, but its regulatory roles remain elusive. Here, on the basis of oG-induced guanine-to-thymine (oG > T) variations featured in sequencing, we discovered widespread position-specific oGs in tumour microRNAs, preferentially oxidized towards 5' end seed regions (positions 2-8) with clustered sequence patterns and clinically associated with patients in lower-grade gliomas and liver hepatocellular carcinoma.

8-Oxoguanine: from oxidative damage to epigenetic and epitranscriptional modification.

In pathophysiology, reactive oxygen species control diverse cellular phenotypes by oxidizing biomolecules. Among these, the guanine base in nucleic acids is the most vulnerable to producing 8-oxoguanine, which can pair with adenine. Because of this feature, 8-oxoguanine in DNA (8-oxo-dG) induces a G > T (C > A) mutation in cancers, which can be deleterious and thus actively repaired by DNA repair pathways.

AGO-accessible anticancer siRNAs designed with synergistic miRNA-like activity.

Small interfering RNAs (siRNAs) therapeutically induce RNA interference (RNAi) of disease-causing genes, but they also silence hundreds of seed-matched off-targets as behaving similar to microRNAs (miRNAs). miRNAs control the pathophysiology of tumors, wherein their accessible binding sites can be sequenced by Argonaute crosslinking immunoprecipitation (AGO CLIP). Herein, based on AGO CLIP, we develop potent anticancer siRNAs utilizing miRNA-like activity (mi/siRNAs).

Quantitative assessment of self-treated canalith repositioning procedures using inertial measurement unit sensors.

Background: Low success and high recurrence of benign paroxysmal positional vertigo (BPPV) after home-based self-treated Epley and Barbeque (BBQ) roll maneuvers is an important issue.

Objective: To quantify the cause of low success rate of self-treated Epley and BBQ roll maneuvers and provide a clinically acceptable criterion to guide self-treatment head rotations.

Methods: Twenty-five participants without active BPPV wore a custom head-mount rotation monitoring device for objective measurements.

Position-specific oxidation of miR-1 encodes cardiac hypertrophy.

In pathophysiology, reactive oxygen species oxidize biomolecules that contribute to disease phenotypes. One such modification, 8-oxoguanine (oG), is abundant in RNA but its epitranscriptional role has not been investigated for microRNAs (miRNAs). Here we specifically sequence oxidized miRNAs in a rat model of the redox-associated condition cardiac hypertrophy.

CLIPick: a sensitive peak caller for expression-based deconvolution of HITS-CLIP signals.

High-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP, also called CLIP-Seq) has been used to map global RNA-protein interactions. However, a critical caveat of HITS-CLIP results is that they contain non-linear background noise-different extent of non-specific interactions caused by individual transcript abundance-that has been inconsiderately normalized, resulting in sacrifice of sensitivity. To properly deconvolute RNA-protein interactions, we have implemented CLIPick, a flexible peak calling pipeline for analyzing HITS-CLIP data, which statistically determines the signal-to-noise ratio for each transcript based on the expression-dependent background simulation.

siAbasic: a comprehensive database for potent siRNA-6Ø sequences without off-target effects.

Small interfering RNA (siRNA) is widely used to specifically silence target gene expression, but its microRNA (miRNA)-like function inevitably suppresses hundreds of off-targets. Recently, complete elimination of the off-target repression has been achieved by introducing an abasic nucleotide to the pivot (position 6; siRNA-6Ø), of which impaired base pairing destabilizes transitional nucleation (positions 2-6). However, siRNA-6Ø varied in its conservation of on-target activity (∼80-100%), demanding bioinformatics to discover the principles underlying its on-target efficiency.

Evaluation and control of miRNA-like off-target repression for RNA interference.

RNA interference (RNAi) has been widely adopted to repress specific gene expression and is easily achieved by designing small interfering RNAs (siRNAs) with perfect sequence complementarity to the intended target mRNAs. Although siRNAs direct Argonaute (Ago), a core component of the RNA-induced silencing complex (RISC), to recognize and silence target mRNAs, they also inevitably function as microRNAs (miRNAs) and suppress hundreds of off-targets. Such miRNA-like off-target repression is potentially detrimental, resulting in unwanted toxicity and phenotypes.

MicroRNA Target Recognition: Insights from Transcriptome-Wide Non-Canonical Interactions.

MicroRNAs (miRNAs) are small non-coding RNAs (∼22 nucleotides) regulating gene expression at the post-transcriptional level. By directing the RNA-induced silencing complex (RISC) to bind specific target mRNAs, miRNA can repress target genes and affect various biological phenotypes. Functional miRNA target recognition is known to majorly attribute specificity to consecutive pairing with seed region (position 2-8) of miRNA.

Rationally designed siRNAs without miRNA-like off-target repression.

Small interfering RNAs (siRNAs) have been developed to intentionally repress a specific gene expression by directing RNA-induced silencing complex (RISC), mimicking the endogenous gene silencer, microRNAs (miRNAs). Although siRNA is designed to be perfectly complementary to an intended target mRNA, it also suppresses hundreds of off-targets by the way that miRNAs recognize targets. Until now, there is no efficient way to avoid such off-target repression, although the mode of miRNA-like interaction has been proposed.

Abasic pivot substitution harnesses target specificity of RNA interference.

Gene silencing via RNA interference inadvertently represses hundreds of off-target transcripts. Because small interfering RNAs (siRNAs) can function as microRNAs, avoiding miRNA-like off-target repression is a major challenge. Functional miRNA-target interactions are known to pre-require transitional nucleation, base pairs from position 2 to the pivot (position 6).

Enhanced attachment of human osteoblasts on NH3-treated poly(L-lactic acid) membranes for guided bone regeneration.

Barrier membranes for guided bone regeneration (GBR) were prepared by a solvent casting method using solutions of poly(L-lactic acid) (PLLA) and chitosan. PLLA and PLLA/chitosan membranes were treated with ammonia gas plasma. PLLA/chitosan membranes were successfully fabricated, and the surface of the PLLA/chitosan membrane was clearly modified by NH3 plasma treatment according to attenuated total reflectance (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) analyses.

A comparative study of bone formation following grafting with different ratios of particle dentin and tricalcium phosphate combinations.

This study aimed to evaluate the bone regeneration relative to tooth powder and tricalcium phosphate (TCP) mixing ratios using the rabbit cranium defect model. The tooth powder was mixed with TCP in 1:1, 3:1, and 1:3 ratios, and the different ratios were implanted in the rabbit cranium defect for 4 and 8 weeks. Powders crystal structure evaluated using scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and new bone formation (NBF) was analyzed using micro-computed tomography (CT) and histologic examination.

The impact of temperament and character on the efficacy of nonpharmacologic treatment of primary insomnia.

Nonpharmacologic treatment, also known as cognitive behavioral treatment, is a first-line treatment of primary insomnia. We aimed to assess factors, including temperament and character, that were associated with responses to nonpharmacologic treatments of primary insomnia, that may assist physicians to recommend appropriate treatment. Outpatients diagnosed with psychophysiological insomnia (n = 99) were recruited between May 2009 and January 2010.

Adenosine and purine nucleosides protect rat primary astrocytes from peroxynitrite-potentiated, glucose deprivation-induced death: preservation of intracellular ATP level.

Previously we have reported that immunostimulated astrocytes became highly vulnerable to glucose deprivation. In the present study we examined the effect of various kinds of nucleosides on the augmented death of glucose-deprived immunostimulated astrocytes. Preincubation with interferon-gamma (100 U/ml) and lipopolysaccharide (1 microg/ml) for 48 h and continuous exposure to glucose deprivation (4 h) significantly induced the lactate dehydrogenase (LDH) release, as a marker of cell injury or death, from astrocytes.