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排序方式: 共有773条查询结果,搜索用时 15 毫秒
611.
Tobias Puengel Sander Lefere Jana Hundertmark Marlene Kohlhepp Christian Penners Frederique Van de Velde Bruno Lapauw Anne Hoorens Lindsey Devisscher Anja Geerts Stephanie Boehm Qihong Zhao John Krupinski Edgar D. Charles Bradley Zinker Frank Tacke 《International journal of molecular sciences》2022,23(12)
(1) Background: With new potential drug targets emerging, combination therapies appear attractive to treat non-alcoholic steatohepatitis (NASH) and fibrosis. Chemokine receptor CCR2/5 antagonists can improve fibrosis by reducing monocyte infiltration and altering hepatic macrophage subsets. Fibroblast growth factor 21 (FGF21) may improve NASH by modulating lipid and glucose metabolism. We compared effects of single drug to combination treatment as therapeutic strategies against NASH. (2) Methods: We analyzed serum samples and liver biopsies from 85 nonalcoholic fatty liver disease (NAFLD) patients. A CCR2/5 inhibitor (BMS-687681-02-020) and a pegylated FGF21 agonist (BMS-986171) were tested in male C57BL/6J mice subjected to dietary models of NASH and fibrosis (choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) up to 12 weeks; short- (2w) or long-term (6w) treatment). (3) Results: In NAFLD patients, chemokine CCL2 and FGF21 serum levels correlated with inflammatory serum markers, only CCL2 was significantly associated with advanced liver fibrosis. In rodent NASH, CCR2/5 inhibition significantly reduced circulating Ly6C+ monocytes and hepatic monocyte-derived macrophages, alongside reduced hepatic inflammation and fibrosis. FGF21 agonism decreased body weight, liver triglycerides and histological NASH activity. Combination treatment reflected aspects of both compounds upon short- and long-term application, thereby amplifying beneficial effects on all aspects of steatohepatitis and fibrosis. (4) Conclusions: CCR2/5 inhibition blocks hepatic infiltration of inflammatory monocytes, FGF21 agonism improves obesity-related metabolic disorders. Combined therapy ameliorates steatohepatitis and fibrosis more potently than single drug treatment in rodent NASH, corroborating the therapeutic potential of combining these two approaches in NASH patients. 相似文献
612.
Natalie Gray Maren M. Limberg Daniela Wiebe Tobias Weihrauch Anna Langner Nicola Brandt Anja U. Bruer Ulrike Raap 《International journal of molecular sciences》2022,23(24)
Basophils are key effector cells in atopic diseases, and the signaling sphingolipid Sphigosine-1-phosphate (S1P) is emerging as an important mediator in these conditions. The possible interaction of S1P and basophils and the resulting biological effects have not yet been studied. We hypothesize that S1P influences the function of basophils in atopy and aim to elucidate the modes of interaction. S1P receptor (S1PR) expression in human peripheral blood basophils from atopic and non-atopic patients was assessed through qRT-PCR and flow cytometry analysis. Functional effects of S1P were assessed through a basophil activation test (BAT), calcium flux, apoptosis, and chemotaxis assays. Immunofluorescence staining was performed to visualize intracellular S1P. Human basophils express S1PR1, S1PR2, S1PR3, and S1PR4 on the mRNA level. 0.1 µM S1P have anti-apoptotic, while 10 µM exhibits apoptotic effects on basophils. Basophils from atopic patients show less chemotactic activity in response to S1P than those from healthy donors. Protein expression of S1PR1 is downregulated in atopic patients, and basophils in lesional AD skin possess intracellular S1P. These findings suggest that the interaction of S1P and basophils might be an important factor in the pathophysiology of atopy. 相似文献
613.
Francesco Brunori Dr. Deepak Kumar Padhi Israel Alshanski Dr. Joanna Freyse Jan-Niklas Dürig Anja Penk Prof. Luigi Vaccaro Dr. Mattan Hurevich Prof. Jörg Rademann Prof. Shlomo Yitzchaik 《Chembiochem : a European journal of chemical biology》2022,23(3):e202100552
Cytokines such as interleukin-8 activate the immune system during infection and interact with sulfated glycosaminoglycans with specific sulfation patterns. In some cases, these interactions are mediated by metal ion binding which can be used to tune surface-based glycan-protein interactions. We evaluated the effect of both hyaluronan sulfation degree and Fe3+ on interleukin-8 binding by electrochemical impedance spectroscopy and surface characterizations. Our results show that sulfation degree and metal ion interactions have a synergistic effect in tuning the electrochemical response of the glycated surfaces to the cytokine. 相似文献
614.
Bernhard Schäfer Felipe Andrés Toro Chacón Thorsten Brinkmann Anja Drews Eberhard Jochem Jörg Sauer 《化学,工程师,技术》2021,93(8):1247-1256
The EDUAR&D methodology, short for energy data and analysis R&D, is used to evaluate energy efficiency technologies. It is a structured research and analysis process, which combines various methodological approaches for the presentation, analysis, and evaluation of the technologies. The aim is to derive recommendations for action, e.g., with regard to thematic priorities, for future energy research within the framework of research funding and recommendations for energy policy. The methodology is presented here using the examples of organic solvent nanofiltration and latent heat storage. 相似文献
615.
The importance of reporting is ever increasing in today’s fast-paced market environments and the availability of up-to-date
information for reporting has become indispensable. Current reporting systems are separated from the online transaction processing
systems (OLTP) with periodic updates pushed in. A pre-defined and aggregated subset of the OLTP data, however, does not provide
the flexibility, detail, and timeliness needed for today’s operational reporting. As technology advances, this separation
has to be re-evaluated and means to study and evaluate new trends in data storage management have to be provided. This article
proposes a benchmark for combined OLTP and operational reporting, providing means to evaluate the performance of enterprise
data management systems for mixed workloads of OLTP and operational reporting queries. Such systems offer up-to-date information
and the flexibility of the entire data set for reporting. We describe how the benchmark provokes the conflicts that are the
reason for separating the two workloads on different systems. In this article, we introduce the concepts, logical data schema,
transactions and queries of the benchmark, which are entirely based on the original data sets and real workloads of existing,
globally operating enterprises. 相似文献
616.
Manly Tom; Dove Anja; Blows Suzy; George Melanie; Noonan MaryAnn P.; Teasdale Thomas W.; Dodds Christopher M.; Fish Jessica; Warburton Elizabeth 《Canadian Metallurgical Quarterly》2009,23(4):519
Unilateral spatial neglect, a debilitating condition affecting awareness of one side of space, is commonly assessed using cancellation tasks in which patients cross out targets distributed over a sheet. Standard scores emphasize the left–right distribution of omissions. Here, the additional value of extracting temporal as well as spatial aspects of performance from video recordings was examined. Videos from 18 patients with left neglect and 19 healthy age-matched control participants were obtained. Interrater reliability of the video analysis was high. In addition to overall differences in target detection and bias, patients significantly differed from the control group in terms of the location of first cancellation, overall slowness, greater variability in speed, systematic slowing with time on task and as a function of target location, less coherent search organization, and a sharply increased tendency to recancel targets. Considering a subset of patients whose scores, by standard criteria, were at or near the normal range indicated that these additional variables indeed increased the sensitivity of the task as well as allowed the simultaneous assessment of spatial and nonspatial aspects of the disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
617.
Anja Reinert Nirav BarapatreSilke Sachse Tilo Reinert 《Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms》2011,269(20):2292-2296
The vinegar fly Drosophila melanogaster is used as model organism to study a variety of different scientific purposes. Thus, our laboratory studies the olfactory system by neurobiological experiments. These techniques are often disruptive and need to compensate or exchange the body fluid, the lymph, with an artificial Ringer’s solution in defined compartments of the fly. The solution mainly contains Na, Cl, K and Ca and is to keep physiological conditions. Therefore, the knowledge about the ion concentrations in the respective Drosophila lymph is required for a correct mixture of the ions.This paper presents the spatially resolved concentrations of P, S, Cl, K, Ca, Fe, Cu and Zn in lyophilised head cryosections of Drosophila by using quantitative μPIXE at the ion beam facility LIPSION in Leipzig. The PIXE maps enable a detailed analysis of particular regions of interest down to a spatial resolution of 0.5 μm.We quantified the ion concentrations especially in the brain, the antenna and its sensilla hairs acting as the olfactory organ of the fly, in the compound eye and in the mouthparts. The averaged element concentrations of these main compartments are (in descending order): P: 90 mM, K: 81 mM, S: 38 mM, Cl: 18 mM, Ca: 4.9 mM, Fe: 1.4 mM, Zn: 1.2 mM, Cu: 0.06 mM. Certain structures or cavities possess a remarkably high concentration of particular elements and might reflect the different functions of the compartments. An example presented in more detail is the composition of the compound eye. Conclusively, our findings on the ion concentrations might be useful for the mixture of the Drosophila Ringer’s solution to ensure physiological conditions in experiments. 相似文献
618.
To overcome the overhead involved with channel estimation, several non-coherent distributed space–time coding (DSTC) strategies for two-way wireless relay networks (TWRNs) using the amplify-and-forward and the decode-and-forward protocol have been recently proposed that do not require channel state information (CSI) at any node to decode the information symbols. In this paper, novel differential DSTC strategies for TWRNs using the two- and three-phase protocol are proposed. In our transmission schemes, the relays do not waste power to transmit information known at the respective destination nodes. This is achieved by combining the symbols from both terminals received at the relays into a single symbol of the unaltered constellation. Furthermore, in our strategies, the direct link between the communicating terminals can be naturally incorporated to further improve the diversity gain. Simulations show a substantially improved performance in terms of bit error rate (BER) of the proposed strategies as compared to the existing strategies. 相似文献
619.
In a bivariate data set it is easy to represent clusters, e.g. by manually circling them or separating them by lines. But many data sets have more than two variables, or they come in the form of inter-object dissimilarities. There exist methods to partition such a data set into clusters, but the resulting partition is not visual by itself. In this paper we construct a new graphical display called CLUSPLOT, in which the objects are represented as points in a bivariate plot and the clusters as ellipses of various sizes and shapes. The algorithm is implemented as an S-PLUS function. Several options are available, e.g. labelling of objects and clusters, drawing lines connecting clusters, and the use of color. We illustrate this new tool with several examples. 相似文献
620.
Tijana Maric Vaios Adamakis Zhongyang Zhang Carmen Milián-Guimerá Lasse Højlund Eklund Thamdrup Eugen Stamate Mahdi Ghavami Anja Boisen 《Small (Weinheim an der Bergstrasse, Germany)》2023,19(15):2206330
In the case of macromolecules and poorly permeable drugs, oral drug delivery features low bioavailability and low absorption across the intestinal wall. Intestinal absorption can be improved if the drug formulation could be transported close to the epithelium. To achieve this, a cascade delivery device comprising Magnesium-based Janus micromotors (MMs) nesting inside a microscale containers (MCs) has been conceptualized. The device aims at facilitating targeted drug delivery mediated by MMs that can lodge inside the intestinal mucosa. Loading MMs into MCs can potentially enhance drug absorption through increased proximity and unidirectional release. The MMs will be provided with optimal conditions for ejection into any residual mucus layer that the MCs have not penetrated. MMS confined inside MCs propel faster in the mucus environment as compared to non-confined MMs. Upon contact with a suitable fuel, the MM-loaded MC itself can also move. An in vitro study shows fast release profiles and linear motion properties in porcine intestinal mucus compared to more complex motion in aqueous media. The concept of dual-acting cascade devices holds great potential in applications where proximity to epithelium and deep mucus penetration are needed. 相似文献