Abstract：
:Gapmer antisense oligonucleotides cleave target RNA effectively in vivo, and is considered as promising therapeutics. Especially, gapmers modified with locked nucleic acid (LNA) shows potent knockdown activity; however, they also cause hepatotoxic side effects. For developing safe and effective gapmer drugs, a deeper understanding of the mechanisms of hepatotoxicity is required. Here, we investigated the cause of hepatotoxicity derived from LNA-modified gapmers. Chemical modification of gapmer's gap region completely suppressed both knockdown activity and hepatotoxicity, indicating that the root cause of hepatotoxicity is related to intracellular gapmer activity. Gene silencing of hepatic ribonuclease H1 (RNaseH1), which catalyses gapmer-mediated RNA knockdown, strongly supressed hepatotoxic effects. Small interfering RNA (siRNA)-mediated knockdown of a target mRNA did not result in any hepatotoxic effects, while the gapmer targeting the same position on mRNA as does the siRNA showed acute toxicity. Microarray analysis revealed that several pre-mRNAs containing a sequence similar to the gapmer target were also knocked down. These results suggest that hepatotoxicity of LNA gapmer is caused by RNAseH1 activity, presumably because of off-target cleavage of RNAs inside nuclei.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Kasuya T,Hori S,Watanabe A,Nakajima M,Gahara Y,Rokushima M,Yanagimoto T,Kugimiya Adoi
10.1038/srep30377subject
Has Abstractpub_date
2016-07-27 00:00:00pages
30377issn
2045-2322pii
srep30377journal_volume
6pub_type
杂志文章abstract：:Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract infection in infants and elderly. To understand the evolution of neutralizing epitopes on the RSV glycoprotein (G) and fusion (F) proteins, we conducted a multi-year surveillance program (OUTSMART-RSV) in the US. Analysis of 1,146 RSV ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-40387-y
更新日期：2019-03-07 00:00:00
abstract：:Recent studies have indicated that different post-translational modifications (PTMs) synergistically orchestrate specific biological processes by crosstalks. However, the preference of the crosstalk among different PTMs and the evolutionary constraint on the PTM crosstalk need further dissections. In this study, the i...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep07331
更新日期：2014-12-05 00:00:00
abstract：:We sequenced coding regions of the cluster of differentiation 36 (CD36) gene in 184 French individuals of European ancestry presenting simultaneously with type 2 diabetes (T2D), arterial hypertension, dyslipidemia, and coronary heart disease. We identified rare missense mutations (p.Pro191Leu/rs143150225 and p.Ala252V...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-53388-8
更新日期：2019-11-20 00:00:00
abstract：:We propose a polarization beam splitter (PBS) with a footprint of only 600 × 790 nm2 operating at a wavelength of λ = 1550 nm, which is the smallest PBS ever demonstrated. This device uses CMOS-compatible materials, namely, silicon and silica. The present PBS comprises two Si waveguides with different geometrical aspe...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-05019-3
更新日期：2017-07-03 00:00:00
abstract：:The digit ratio has been used as a retrospective noninvasive biomarker to investigate the putative effects of prenatal exposure to androgens. In recent years, many scholars have paid attention to the association between 2D:4D (the second and fourth digits) and prostatic cancer. This study explored the prognostic signi...
journal_title：Scientific reports
pub_type： 杂志文章,多中心研究
doi：10.1038/s41598-017-05638-w
更新日期：2017-07-12 00:00:00
abstract：:Alterations in the gut microbiome have been reported in liver cirrhosis, and probiotic interventions are considered a potential treatment strategy. This study aimed to evaluate the effects and mechanisms of Lactobacillus salivarius LI01, Pediococcus pentosaceus LI05, Lactobacillus rhamnosus GG, Clostridium butyricum M...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-07091-1
更新日期：2017-07-31 00:00:00
abstract：:Skyrmions in ultrathin ferromagnetic metal (FM)/heavy metal (HM) multilayer systems produced by conventional sputtering methods have recently generated huge interest due to their applications in the field of spintronics. The sandwich structure with two correctly-chosen heavy metal layers provides an additive interfaci...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-23799-0
更新日期：2018-04-09 00:00:00
abstract：:The need for sensitive, robust, portable, and inexpensive biosensing platforms is of significant interest in clinical applications for disease diagnosis and treatment monitoring at the point-of-care (POC) settings. Rapid, accurate POC diagnostic assays play a crucial role in developing countries, where there are limit...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep08719
更新日期：2015-03-06 00:00:00
abstract：:Calcium oxalate monohydrate (COM) crystals cause kidney stone disease by still unclear mechanisms. The present study aimed to characterize changes in secretion of proteins from basolateral compartment of renal tubular epithelial cells after exposure to COM crystals and then correlated them with the stone pathogenesis....
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep24064
更新日期：2016-04-05 00:00:00
abstract：:One of the greatest challenges in the field of biofabrication remains the discovery of suitable bioinks that satisfy physicochemical and biological requirements. Despite recent advances in tissue engineering and biofabrication, progress has been limited to the development of technologies using polymer-based materials....
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-59632-w
更新日期：2020-02-18 00:00:00
abstract：:CSNK2B, which encodes the beta subunit of casein kinase II (CK2), plays an important role in neuron morphology and synaptic transmission. Variants in CSNK2B associated with epilepsy and/or intellectual disability (ID)/developmental delay (DD) have been reported in five cases only. Among the 816 probands suspected here...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-53484-9
更新日期：2019-11-29 00:00:00
abstract：:Hepatitis C virus (HCV) infection of hepatocytes promotes liver fibrosis by activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix in liver tissue. Whether or not host factors released from the HCV-infected hepatocytes play role in HSCs activation is unclear. In this study, HSCs w...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-04259-7
更新日期：2017-06-30 00:00:00
abstract：:Attending a location in space facilitates responses to targets at that location when the time between cue and target is short. Certain types of exogenous cues - such as sudden peripheral onsets - have been described as reflexive and automatic. Recent studies however, have been showing many cases where exogenous cues a...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-31633-w
更新日期：2018-09-05 00:00:00
abstract：:Nitric oxide (NO) is an important signalling molecule involved in haemostasis. NO, present as endogenous S-nitrosothiols, is released by cysteine through a transnitrosation reaction. To exploit this mechanism, cysteine was immobilised onto the different carboxylated polyethylene terephthalate (PET) surfaces using 1-st...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-53108-2
更新日期：2019-11-13 00:00:00
abstract：:The transparency of animals is an important biological feature. Ascidian eggs have various degrees of transparency, but this characteristic has not yet been measured quantitatively and comprehensively. In this study, we established a method for evaluating the transparency of eggs to first characterize the transparency...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-77585-y
更新日期：2020-11-30 00:00:00
abstract：:The quality of avian semen is an important economic trait in poultry production. The present study examines the in vitro effects of non-thermal dielectric barrier discharge plasma on chicken sperm to determine the plasma conditions that can produce the optimum sperm quality. Exposure to 11.7 kV of plasma for 20 s is f...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-26049-5
更新日期：2018-05-15 00:00:00
abstract：:Vanadium doped ZnO (VZO) thin films were grown by RF magnetron sputtering, starting from a ZnO:V ceramic target. The crystal structure, chemical composition, electric and piezoelectric properties of the films were investigated either on the as-grown thin films or after a post-deposition rapid thermal annealing (RTA) t...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep41957
更新日期：2017-02-06 00:00:00
abstract：:The phylogenetic characteristics of microbial communities associated with periodontitis have been well studied, however, little is known about the functional endowments of this ecosystem. The present study examined 73 microbial assemblages from 25 individuals with generalized chronic periodontitis and 25 periodontally...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep38993
更新日期：2016-12-19 00:00:00
abstract：:The clinical application of dihydroartemisinin (DHA) has been hampered due to its poor water-solubility. To overcome this hurdle, we devised a novel polymer-drug conjugate, multiarm polyethylene glycol-dihydroartemisinin (PEG-DHA), made by linking DHA with multiarm polyethylene glycol. Herein, we investigated PEG-DHA ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep05871
更新日期：2014-07-29 00:00:00
abstract：:What's on the label is not what's in the bottle, from food products to herbal medicinal products (HMPs), economically-motivated biomaterials adulteration is a long-term problem affecting the food and drug industry. Accurate identification of the biomaterial ingredients in processed commodities is highly desirable. In ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-05083-9
更新日期：2017-07-06 00:00:00
abstract：:The stethoscope is used as first line diagnostic tool in assessment of patients with pulmonary symptoms. However, there is much debate about the diagnostic accuracy of this instrument. This meta-analysis aims to evaluate the diagnostic accuracy of lung auscultation for the most common respiratory pathologies. Studies ...
journal_title：Scientific reports
pub_type： 杂志文章,meta分析
doi：10.1038/s41598-020-64405-6
更新日期：2020-04-30 00:00:00
abstract：:The incidence of myopia is increasing worldwide, and the investigation on pathophysiology of myopia is becoming more important. This retrospective study aimed to compare the thicknesses of individual retinal layers between high-myopic and control eyes, and to evaluate the effects of age and sex on each retinal layer t...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-50306-w
更新日期：2019-09-30 00:00:00
abstract：:Modeling the dynamic nature of protein-ligand binding with atomistic simulations is one of the main challenges in computational biophysics, with important implications in the drug design process. Although in the past few years hardware and software advances have significantly revamped the use of molecular simulations,...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-08445-5
更新日期：2017-08-16 00:00:00
abstract：:A robust method is presented for the segmentation of the full cerebral vasculature in 4-dimensional (4D) computed tomography (CT). The method consists of candidate vessel selection, feature extraction, random forest classification and postprocessing. Image features include among others the weighted temporal variance i...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-15617-w
更新日期：2017-11-15 00:00:00
abstract：:Anatomically realistic organ replicas or phantoms allow for accurate studies and reproducible research. To recreate a human kidney, mimicry of the elastic properties of the human kidney is crucial. However, none of the related work addressed the design and development of a kidney phantom using only silicone as materia...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-68886-3
更新日期：2020-07-16 00:00:00
abstract：:The role of the different lymphocyte populations in liver microenvironment of chronic hepatitis C (CHC) patients is still matter of debate. Since Th17 and Treg have opposite functions, their balance could affect disease progression. The aim was to explore liver microenvironment and its peripheral blood counterpart in ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-13777-3
更新日期：2017-10-16 00:00:00
abstract：:Multinational corporations use highly complex structures of parents and subsidiaries to organize their operations and ownership. Offshore Financial Centers (OFCs) facilitate these structures through low taxation and lenient regulation, but are increasingly under scrutiny, for instance for enabling tax avoidance. There...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-06322-9
更新日期：2017-07-24 00:00:00
abstract：:Impedance, or oscillometry, measurements of the respiratory system can generate information about the function of the respiratory system not possible with traditional spirometry. There are currently several instruments on the market using different perturbations. We have compared a new respiratory oscillometry instrum...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-48039-x
更新日期：2019-08-12 00:00:00
abstract：:The phytohormone auxin is a major determinant and regulatory component important for plant development. Auxin transport between cells is mediated by a complex system of transporters such as AUX1/LAX, PIN, and ABCB proteins, and their localization and activity is thought to be influenced by phosphatases and kinases. Fl...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep41906
更新日期：2017-02-06 00:00:00
abstract：:Transplantation of human bone marrow mesenchymal stromal cells (hBM-MSC) promotes functional recovery after stroke in animal models, but the mechanisms underlying these effects remain incompletely understood. We tested the efficacy of Good Manufacturing Practices (GMP) compliant hBM-MSC, injected intravenously 3.5 hou...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-07274-w
更新日期：2017-07-31 00:00:00
