Abstract：
:Diseases and toxins may lead to death of active liver tissue, resulting in a loss of total clearance capacity at the whole-body level. However, it remains difficult to study, whether the loss of metabolizing tissue is sufficient to explain loss of metabolic capacity of the liver or whether the surviving tissue undergoes an adaptive response to compensate the loss. To understand the cellular impact of toxic liver damage in an in vivo situation, we here used physiologically-based pharmacokinetic modelling to investigate pharmacokinetics of a specifically designed drug cocktail at three different sampling sites of the body in healthy mice and mice treated with carbon tetrachloride (CCl4). Liver zonation was explicitly quantified in the models through immunostaining of cytochrome P450s enzymes. Comparative analyses between the simulated decrease in clearance capacity and the experimentally measured loss in tissue volume indicated that CCl4-induced impairment of metabolic functions goes beyond the mere loss of metabolically active tissue. The here established integrative modelling strategy hence provides mechanistic insights into functional consequences of toxic liver damage in an in vivo situation, which would not have been accessible by conventional methods.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Schenk A,Ghallab A,Hofmann U,Hassan R,Schwarz M,Schuppert A,Schwen LO,Braeuning A,Teutonico D,Hengstler JG,Kuepfer Ldoi
10.1038/s41598-017-04574-zsubject
Has Abstractpub_date
2017-07-24 00:00:00pages
6224issue
1issn
2045-2322pii
10.1038/s41598-017-04574-zjournal_volume
7pub_type
杂志文章abstract：:AMP-activated protein kinase (AMPK) is a key sensor and regulator of glucose metabolism. Here, we demonstrated that shizukaol F, a natural compound isolated from Chloranthus japonicus, can activate AMPK and modulate glucose metabolism both in vitro and in vivo. Shizukaol F increased glucose uptake in differentiated C2...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-00925-y
更新日期：2017-04-10 00:00:00
abstract：:Interleukin-10 (IL-10) plays a central role in regulation of intestinal mucosal homeostasis and prevention of inflammatory bowel disease (IBD). We previously reported that CD11b(hi) regulatory dendritic cells (DCs) can produce more IL-10, and CD11b can negatively regulate Toll-like receptors (TLRs)-induced inflammator...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep26252
更新日期：2016-05-18 00:00:00
abstract：:Horseradish peroxidase (HRP) mediates efficient conversion of many phenolic contaminants and thus has potential applications for pollution control. Such potentially important applications suffer however from the fact that the enzyme becomes quickly inactivated during phenol oxidation and polymerization. The work here ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep03126
更新日期：2013-11-04 00:00:00
abstract：:For accurate micro-scale quantification of a specific protein in biological fluids, immunoaffinity chromatography (IAC) and isoelectric focusing (IEF) were combined in a single fused-silica capillary. The inner wall of the capillary was coated with an anti-E-tag antibody at the inlet side to form an IAC column, and po...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep39221
更新日期：2016-12-15 00:00:00
abstract：:Despite aggressive antimicrobial therapy, many respiratory pathogens persist in the lung, underpinning the chronic inflammation and eventual lung decline that are characteristic of respiratory disease. Recently, bile acid aspiration has emerged as a major comorbidity associated with a range of lung diseases, shaping t...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep29768
更新日期：2016-07-19 00:00:00
abstract：:Adenoviruses are very efficient vectors for delivering therapeutic genes in preclinical and clinical trials. However, randomized controlled human trials have often been lacking clear clinically relevant results. We hypothesized that high lipid levels and specific lipoproteins could significantly decrease adenoviral tr...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-00376-5
更新日期：2017-03-24 00:00:00
abstract：:Protein phosphorylation is an important type of post-translational modification that is involved in a variety of biological activities. Most phosphorylation events occur on serine, threonine and tyrosine residues in eukaryotes. In recent years, many phosphorylation sites have been identified as a result of advances in...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep24735
更新日期：2016-04-19 00:00:00
abstract：:YPEL3 that induces cellular senescence in both normal and tumour cells of humans may show altered expression under the influence of incidental mutations. In this study, we proposed the first structure of Native YPEL3 protein and its five possible deleterious mutants-V40M, C61Y, G98R, G108S, and A131T and predicted the...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-72333-8
更新日期：2020-09-17 00:00:00
abstract：:Although intestinal trefoil factor (ITF) can alleviate the burn-induced intestinal mucosa injury, the underlying mechanisms remains elusive. In this study, we investigated if ITF alters glutamine transport on the brush border membrane vesicles (BBMVs) of the intestines in Sprague-Dawley rats inflicted with 30% TBSA an...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-21282-4
更新日期：2018-02-16 00:00:00
abstract：:Tumorigenesis is driven by genetic alterations that perturb the signaling networks regulating proliferation or cell death. In order to block tumor growth, one has to precisely know how these signaling pathways function and interplay. Here, we identified the transcription factor Ets21C as a pivotal regulator of tumor g...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep34725
更新日期：2016-10-07 00:00:00
abstract：:HMG domain transcription factor, Sox2, is a critical gene for the development of cochlear hair cells, the receptor cells for hearing, but this has been ascribed to expansion of the progenitors that become hair cells. Here, we show that Sox2 activated Atoh1, a transcription factor important for hair cell differentiatio...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep23293
更新日期：2016-03-18 00:00:00
abstract：:We report on high-performance thermochromic ZrO2/V0.982W0.018O2/ZrO2 coatings with a low transition temperature prepared on glass by a low-temperature scalable deposition technique. The V0.982W0.018O2 layers were deposited by a controlled high-power impulse magnetron sputtering of V target, combined with a simultaneou...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-68002-5
更新日期：2020-07-06 00:00:00
abstract：:Multi-domain voltage-gated ion channels appear to have evolved through sequential rounds of intragenic duplication from a primordial one-domain precursor. Whereas modularity within one-domain symmetrical channels is established, little is known about the roles of individual regions within more complex asymmetrical cha...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep38426
更新日期：2016-12-12 00:00:00
abstract：:Emerging evidence suggests that the mammalian target of rapamcyin (mTOR) pathway is associated with radio-resistance in cancer treatment. We hypothesised that phosphorylated ribosomal S6 kinase 1 (p-S6K1), a major downstream regulator of the mTOR pathway, may play a role in predicting radio-resistance. Therefore, we e...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-57496-8
更新日期：2020-01-20 00:00:00
abstract：:The ability to revitalize and re-purpose existing drugs offers a powerful approach for novel treatment options against Mycobacterium tuberculosis and other infectious agents. Antifolates are an underutilized drug class in tuberculosis (TB) therapy, capable of disrupting the biosynthesis of tetrahydrofolate, an essenti...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep38083
更新日期：2016-12-01 00:00:00
abstract：:The inward rectifier Kir2.1 current (IKir2.1) was reported to be facilitated by fluid flow. However, the mechanism underlying this facilitation remains uncertain. We hypothesized that during K+ influx or efflux, [K+] adjacent to the outer mouth of the Kir2.1 channel might decrease or increase, respectively, compared w...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep39585
更新日期：2016-12-22 00:00:00
abstract：:In situ tissue engineering within a stroke cavity is gradually emerging as a novel therapeutic paradigm. Considering the varied lesion topology within each subject, the placement and distribution of cells within the lesion cavity is challenging. The use of multiple cell types to reconstruct damaged tissue illustrates ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep14597
更新日期：2015-09-30 00:00:00
abstract：:Prasinophytes are a paraphyletic group of nine lineages of green microalgae that are currently classified either at the class or order level or as clades without formal taxonomic description. Prasinophyte clade VII comprises picoplanktonic algae that are important components of marine phytoplankton communities, partic...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-12412-5
更新日期：2017-10-25 00:00:00
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 AA...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-43459-1
更新日期：2019-05-06 00:00:00
abstract：:We analytically and numerically investigate magneto-plasmons in metal films surrounded by a ferromagnetic dielectric. In such waveguide using a metal film with a thickness exceeding the Skin depth, an external magnetic field in the transverse direction can induce a significant spatial asymmetry of mode distribution. S...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-28567-8
更新日期：2018-07-12 00:00:00
abstract：:Transport of tissue-derived lymphatic fluid and clearance by draining lymph nodes are pivotal for maintenance of fluid homeostasis in the body and for immune-surveillance of the self- and non-self-proteomes. Yet a quantitative analysis of nodal filtration of the tissue-derived proteome present in lymphatic fluid has n...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-018-29614-0
更新日期：2018-07-26 00:00:00
abstract：:While the worldwide standardization of agricultural production has been advocated and recommended, relatively little research has focused on the ecological significance of such a shift. The ecological concerns stemming from the standardization of agricultural production may require new methodology. In this study, we c...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep21675
更新日期：2016-02-22 00:00:00
abstract：:Reactive Intermediate Deaminase (Rid) protein superfamily includes eight families among which the RidA is conserved in all domains of life. RidA proteins accelerate the deamination of the reactive 2-aminoacrylate (2AA), an enamine produced by some pyridoxal phosphate (PLP)-dependent enzymes. 2AA accumulation inhibits ...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-66663-w
更新日期：2020-06-23 00:00:00
abstract：:Rheumatoid arthritis is characterised by synovial inflammation and proliferation of fibroblast-like synoviocytes. The induction of apoptosis has long been proposed as a target for proliferative autoimmune diseases, and has further been shown to act as a successful treatment of experimental models of arthritis, such as...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep31441
更新日期：2016-08-11 00:00:00
abstract：:The prognostic factors for survival among patients with secondary osteosarcoma remain unclear. The aim of this study was to develop a practical nomogram for predicting cancer-specific survival (CSS) in patients with osteosarcoma as a secondary malignancy. The surveillance, epidemiology, and end results database was us...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-69740-2
更新日期：2020-07-30 00:00:00
abstract：:Absolute numbers of lymphocytes are decreased in uninfected infants born to HIV-1-infected women (HIV-1-exposed). Although the exact mechanism is unknown, fetal exposure to maternal HIV-1-infection could prime the immune system and affect T cell trafficking. We compared the expression of chemokine receptors on cord bl...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep06690
更新日期：2014-10-24 00:00:00
abstract：:The identification of clinically-relevant early diagnostic and prognostic protein biomarkers is essential to maximize therapeutic efficacy and prevent cancer progression. The aim of the current study is to determine whether aberrant plasma protein profile can be applied as a surrogate tool for early diagnosis of bladd...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-020-67929-z
更新日期：2020-07-03 00:00:00
abstract：:Among atrial fibrillation (AF) patients, Danish nationwide registries (2011-2015) were used to examine temporal trends of initiation patterns of oral anticoagulation (OAC) treatment according to age. Overall, 43,299 AF patients initiating vitamin K antagonists (VKA) (42%), dabigatran (29%), rivaroxaban (13%), or apixa...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep31477
更新日期：2016-08-11 00:00:00
abstract：:Emergence of drug-resistant strains of the pathogen Mycobacterium tuberculosis (Mtb) and the ineffectiveness of BCG in curtailing Mtb infection makes vaccine development for tuberculosis an important objective. Identifying immunogenic CD8+ T cell peptide epitopes is necessary for peptide-based vaccine strategies. We p...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep04632
更新日期：2014-04-23 00:00:00
abstract：:To explore the predictive performance of machine learning on the recurrence of patients with gastric cancer after the operation. The available data is divided into two parts. In particular, the first part is used as a training set (such as 80% of the original data), and the second part is used as a test set (the remai...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-021-81188-6
更新日期：2021-01-15 00:00:00
