Abstract:
:Familial hypercholesterolemia (FH) is an inherited disease of lipoprotein metabolism caused by a defect in the LDL receptor (LDLR) leading to severe hypercholesterolemia, and associated with an increased risk of coronary heart disease and myocardial infarction. We have developed a gene therapy protocol for FH using AAV2, AAV9 and lentiviral vectors and tested safety and efficacy in LDL receptor deficient Watanabe Heritable Hyperlipidemic rabbits. We show that LV-LDLR produced a significant long-lasting decrease in total serum cholesterol whereas AAV9-LDLR resulted only in a transient decrease and AAV2-LDLR failed to reduce serum cholesterol levels. A significant pathological side effect, bile-duct proliferation, was seen in the liver of AAV2-LDLR rabbits associated with an increased expression of Cyr61 matricellular protein. Special attention should be given to liver changes in gene therapy applications when genes affecting cholesterol and lipoprotein metabolism are used for therapy.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Hytönen E,Laurema A,Kankkonen H,Miyanohara A,Kärjä V,Hujo M,Laham-Karam N,Ylä-Herttuala Sdoi
10.1038/s41598-019-43459-1subject
Has Abstractpub_date
2019-05-06 00:00:00pages
6934issue
1issn
2045-2322pii
10.1038/s41598-019-43459-1journal_volume
9pub_type
杂志文章abstract::An impairment of cardiac function is a key feature of the cardiovascular failure associated with sepsis. Although there is some evidence that suppression of sarcoplasmic reticulum Ca2+-ATP-ase (SERCA2) contributes to septic cardiomyopathy, it is not known whether prevention of the down-regulation of SERCA2 improves ou...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep37277
更新日期:2016-11-17 00:00:00
abstract::This study aimed to observe the morphological characteristics of a PGLA [poly(glycolide-co-L-lactide)] nerve conduit and regenerated nerve bundle in the human body using high-frequency ultrasound and examine functional recovery of the regenerated nerve using functional magnetic resonance imaging (fMRI) after neural pr...
journal_title:Scientific reports
pub_type: 临床试验,杂志文章
doi:10.1038/srep46403
更新日期:2017-04-13 00:00:00
abstract::We report the temperature dependence of the dielectric function ε = ε1 + iε2 and critical point (CP) energies of biaxial α-SnS in the spectral energy region from 0.74 to 6.42 eV and temperatures from 27 to 350 K using spectroscopic ellipsometry. Bulk SnS was grown by temperature gradient method. Dielectric response fu...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-75383-0
更新日期:2020-10-27 00:00:00
abstract::Novel strategies to target Trypanosoma brucei, Trypanosoma cruzi and Leishmania are urgently needed to generate better and safer drugs against Human African Trypanosomiasis, Chagas disease and Leishmaniasis, respectively. Here, we investigated the feasibility of selectively targeting in trypanosomatids the ubiquitin E...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-52618-3
更新日期:2019-11-07 00:00:00
abstract::Previous reports on epigenetic mechanisms involved in alcohol abuse have focus on hepatic and neuronal regions, leaving the immune system and specifically monocyte-derived dendritic cells (MDDCs) understudied. Our lab has previously shown histone deacetylases are modulated in cells derived from alcohol users and after...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-11172-6
更新日期:2017-09-11 00:00:00
abstract::Awe, a complex emotion composed by the appraisal components of vastness and need for accommodation, is a profound and often meaningful experience. Despite its importance, psychologists have only recently begun empirical study of awe. At the experimental level, a main issue concerns how to elicit high intensity awe exp...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-01242-0
更新日期:2017-04-27 00:00:00
abstract::Photonic qubits lie at the heart of quantum information technology, often encoding information in their polarization state. So far, only low-frequency optical and infrared photons have been employed as flying qubits, as the resources that are at present easiest to control. With their essentially different way of inter...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep25136
更新日期:2016-04-27 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::The benefits that physical exercise confers on cardiovascular health are well known, whereas the notion that physical exercise can also improve cognitive performance has only recently begun to be explored and has thus far yielded only controversial results. In the present study, we used a sample of young male subjects...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep25440
更新日期:2016-05-05 00:00:00
abstract::Lactic acid bacteria (LAB) are the common probiotics. Here, we investigated the antiviral protective effects of heat-killed LAB strain Lactobacillus casei DK128 (DK128) on influenza viruses. Intranasal treatment of mice with DK128 conferred protection against different subtypes of influenza viruses by lessening weight...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-17487-8
更新日期:2017-12-12 00:00:00
abstract::Adipose tissue hyperplasia with increased number of adipocytes is implicated in a protective rather than deleterious effect on obesity-associated metabolic disorder. It is poorly understood how the adipose tissue cellularity is regulated. Tc1 is a gene of vertebrates that regulates diverse downstream genes. Young Tc1-...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep35884
更新日期:2016-10-24 00:00:00
abstract::Antimicrobial peptides (AMPs) are peptide antibiotics with a broad spectrum of antimicrobial activities. Activity prediction of AMPs from their amino acid sequences is of great therapeutic importance but imposes challenges on prediction methods due to label interactions. In this paper we propose a novel multi-label le...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-01986-9
更新日期:2017-05-19 00:00:00
abstract::Oral submucous fibrosis (OSF), regarded as a precancerous condition, is characterized by juxta-epithelial inflammatory reaction followed by fibro-elastic change in the lamina properia and epithelial atrophy. The pathologic mechanisms of OSF still need to be further clarified. In the study, we investigated the function...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep37004
更新日期:2016-11-15 00:00:00
abstract::Externally manipulating memories by presenting conditioned stimuli (CS) during sleep is a new approach to investigating memory processing during sleep. However, whether presenting a CS during REM or NREM sleep enhances or extinguishes fear memory has not been clearly delineated. In this study, mice underwent trace fea...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep46247
更新日期:2017-04-12 00:00:00
abstract::Lithium vanadium phosphate (Li3V2(PO4)3, LVP)/reduced graphene oxide (rGO) composite is prepared with a rheological method followed by heat treatment. The size and interface of LVP particles, two important merits for a cathode material, can be effectively tuned by the rGO in the composite, which plays as surfactant to...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep05768
更新日期:2014-08-29 00:00:00
abstract::microRNAs are an abundant class of small non-coding RNAs that control gene expression post-transcriptionally. Importantly, microRNA activity participates in the regulation of cellular processes and is a potentially valuable source of biomarkers in the diagnosis and prognosis of human diseases. Here we introduce miQPCR...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep11590
更新日期:2015-06-25 00:00:00
abstract::The oral microbiota change dramatically with each part of the oral cavity, even within the same mouth. Nevertheless, the microbiota associated with peri-implantitis and periodontitis have been considered the same. To improve our knowledge of the different communities of complex oral microbiota, we compared the microbi...
journal_title:Scientific reports
pub_type: 杂志文章,meta分析
doi:10.1038/srep06602
更新日期:2014-10-13 00:00:00
abstract::Colon cancer stem cells have been attributed to poor prognosis, therapeutic resistance and aggressive nature of the malignancy. Recent reports associated CD44v6 expression with relapse, metastasis and reduced 5-year survival of colon cancer patients, thereby making it a potential therapeutic target. Thus, in this stud...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-35069-0
更新日期:2018-11-19 00:00:00
abstract::Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to overcome tyrosine kinase inhibitor (TKI) resistance in epithelial growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) cells in vivo and in vitro. However, little is known about the putative induction of no...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-57707-2
更新日期:2020-01-22 00:00:00
abstract::Computed Tomography derived Fractional Flow Reserve (CTFFR) is an emerging non-invasive imaging modality to assess functional significance of coronary stenosis. We performed a meta-analysis to compare the diagnostic performance of CTFFR to invasive Fractional Flow reserve (FFR). Electronic search was performed to iden...
journal_title:Scientific reports
pub_type: 杂志文章,meta分析
doi:10.1038/s41598-018-29910-9
更新日期:2018-08-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-019-54255-2
更新日期:2019-11-21 00:00:00
abstract::Although the search for quantitative trait loci for behaviour remains a considerable challenge, the complicated genetic architecture of quantitative traits is beginning to be understood. The current project utilised heterogeneous stock (HS) male mice (n = 580) to investigate the genetic basis for brain weights, activi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep41204
更新日期:2017-02-01 00:00:00
abstract::Many organisms faced with seasonally fluctuating abiotic and biotic conditions respond by altering their phenotype to account for the demands of environmental changes. Here we discovered that newts, which switch seasonally between an aquatic and terrestrial lifestyle, grow a complex adhesive system on their tongue pad...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-00674-y
更新日期:2017-04-21 00:00:00
abstract::A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper. ...
journal_title:Scientific reports
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41598-018-20340-1
更新日期:2018-01-23 00:00:00
abstract::Many established inflammation- and nutrition-related factors have been investigated as potential independent prognostic factors in various cancers, including the C-reactive protein/albumin ratio (CAR), lymphocyte/monocyte ratio (LMR), modified Glasgow prognostic score (mGPS), body mass index (BMI), and prognostic nutr...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-10328-8
更新日期:2017-08-25 00:00:00
abstract::Systemic antioxidative status has been implicated in glaucoma pathogenesis. Additionally, corneal hysteresis (CH) may contribute to glaucoma progression. Here, we evaluated the relationship between biological antioxidant potential (BAP) and CH. This study included 103 patients with open-angle glaucoma (OAG). We used a...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-57520-x
更新日期:2020-01-17 00:00:00
abstract::Successful tissue repair requires the activities of myeloid cells such as monocytes and macrophages that guide the progression of inflammation and healing outcome. Immunoregenerative materials leverage the function of endogenous immune cells to orchestrate complex mechanisms of repair; however, a deeper understanding ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-00477-1
更新日期:2017-03-27 00:00:00
abstract::A new kind of magnetically-doped antiferromagnetic (AFM) topological insulators (TIs) with stoichiometry Bi1.09Gd0.06Sb0.85Te3 has been studied by angle-resolved photoemission spectroscopy (ARPES), superconducting magnetometry (SQUID) and X-ray magnetic circular dichroism (XMCD) with analysis of its electronic structu...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-41137-w
更新日期:2019-03-18 00:00:00
abstract::The ability of metasurfaces to manipulate light at the subwavelength scale offers unprecedented functionalities for passive and active lasing devices. However, applications of metasurfaces to optical devices are rare due to fabrication difficulties. Here, we present quantum dot light emitting diodes (QDLEDs) with a me...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-15254-3
更新日期:2017-11-07 00:00:00
abstract::Scrapie is a lethal neurodegenerative disease of sheep and goats caused by the misfolding of the prion protein. Variants such as M142, D145, S146, H154, Q211, and K222 were experimentally found to increase resistance or extend scrapie incubation period in goats. We aimed to identify polymorphisms in the Afar and Arsi-...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-63874-z
更新日期:2020-04-24 00:00:00