98 research outputs found

    Resveratrol mediated modulation of Sirt-1/Runx2 promotes osteogenic differentiation of mesenchymal stem cells: potential role of Runx2 deacetylation.

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    Osteogenic repair in response to bone injury is characterized by activation and differentiation of mesenchymal stem cells (MSCs) to osteoblasts. This study determined whether activation of Sirt-1 (a NAD(+)-dependent histone deacetylase) by the phytoestrogen resveratrol affects osteogenic differentiation. Monolayer and high-density cultures of MSCs and pre-osteoblastic cells were treated with an osteogenic induction medium with/without the Sirt-1 inhibitor nicotinamide or/and resveratrol in a concentration dependent manner. MSCs and pre-osteoblastic cells differentiated to osteoblasts when exposed to osteogenic-induction medium. The osteogenic response was blocked by nicotinamide, resulting in adipogenic differentiation and expression of the adipose transcription regulator PPAR-γ (peroxisome proliferator-activated receptor). However, in nicotinamide-treated cultures, pre-treatment with resveratrol significantly enhanced osteogenesis by increasing expression of Runx2 (bone specific transcription factor) and decreasing expression of PPAR-γ. Activation of Sirt-1 by resveratrol in MSCs increased its binding to PPAR-γ and repressed PPAR-γ activity by involving its cofactor NCoR (nuclear receptor co-repressor). The modulatory effects of resveratrol on nicotinamide-induced expression of PPAR-γ and its cofactor NCoR were found to be mediated, at least in part, by Sirt-1/Runx2 association and deacetylation of Runx2. Finally, knockdown of Sirt-1 by using antisense oligonucleotides downregulated the expression of Sirt-1 protein and abolished the inhibitory effects of resveratrol, namely nicotinamide-induced Sirt-1 suppression and Runx2 acetylation, suggesting that the acetylated content of Runx2 is related to downregulated Sirt-1 expression. These data support a critical role for Runx2 acetylation/deacetylation during osteogenic differentiation in MSCs in vitro. (242 words in abstract)

    IGF-1 and PDGF-bb suppress IL-1β-induced cartilage degradation through down-regulation of NF-κB signaling: involvement of Src/PI-3K/AKT pathway.

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    Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that plays a key role in the pathogenesis of osteoarthritis (OA). Growth factors (GFs) capable of antagonizing the catabolic actions of cytokines may have therapeutic potential in the treatment of OA. Herein, we investigated the potential synergistic effects of insulin-like growth factor (IGF-1) and platelet-derived growth factor (PDGF-bb) on different mechanisms participating in IL-1β-induced activation of nuclear transcription factor-κB (NF-κB) and apoptosis in chondrocytes. Primary chondrocytes were treated with IL-1β to induce dedifferentiation and co-treated with either IGF-1 or/and PDGF-bb and evaluated by immunoblotting and electron microscopy. Pretreatment of chondrocytes with IGF-1 or/and PDGF-bb suppressed IL-1β-induced NF-κB activation via inhibition of IκB-α kinase. Inhibition of IκB-α kinase by GFs led to the suppression of IκB-α phosphorylation and degradation, p65 nuclear translocation and NF-κB-regulated gene products involved in inflammation and cartilage degradation (COX-2, MMPs) and apoptosis (caspase-3). GFs or BMS-345541 (specific inhibitor of the IKK) reversed the IL-1β-induced down-regulation of collagen type II, cartilage specific proteoglycans, β1-integrin, Shc, activated MAPKinase, Sox-9 and up-regulation of active caspase-3. Furthermore, the inhibitory effects of IGF-1 or/and PDGF-bb on IL-1β-induced NF-κB activation were sensitive to inhibitors of Src (PP1), PI-3K (wortmannin) and Akt (SH-5), suggesting that the pathway consisting of non-receptor tyrosine kinase (Src), phosphatidylinositol 3-kinase and protein kinase B must be involved in IL-1β signaling. The results presented suggest that IGF-1 and PDGF-bb are potent inhibitors of IL-1β-mediated activation of NF-κB and apoptosis in chondrocytes, may be mediated in part through suppression of Src/PI-3K/AKT pathway, which may contribute to their anti-inflammatory effects

    Ultrafast spin dynamics: complementing theoretical analyses by quantum-information measures

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    Theoretical analyses of ultrafast spin dynamics commonly address and discuss simulated phenomena by means of observables, whereas in quantum information theory one often utilizes measures of quantum states. In this Paper we report on possible benefits of quantum information measures in simulations of ultrafast spin dynamics. For Co/Cu heterostructures illuminated by femtosecond laser pulses, we discuss the general behaviour of quantum information measures, in particular distances in Hilbert space and degrees of mixing in the density matrix. The measures are in particular sensitive to variations of the polarization of a laser pulse and the sample composition. Moreover, they are closely related to magnetization and number of excited electrons

    Ultrafast Dynamics of Orbital Angular Momentum of Electrons Induced by Femtosecond Laser Pulses: Generation and Transfer Across Interfaces

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    The orbital angular momenta (OAM) of electrons play an increasingly important role in ultrafast electron and magnetization dynamics. In this theoretical study, we investigate the electron dynamics induced by femtosecond laser pulses in a normal metal, a ferromagnet, and a ferromagnet/normal metal heterostructure. We analyze the spatio-temporal distributions of the laser-induced OAM and their respective currents. Our findings demonstrate that a circularly polarized laser pulse can induce a sizable and long-lasting OAM component in a normal metal. Furthermore, an interface between a ferromagnet and a normal metal facilitates the demagnetization of the magnet by the OAM contribution to the total magnetization. Finally, to transfer OAM from a ferromagnet into a normal metal, it is advantageous to use a laser setup that induces the desired OAM component in the ferromagnet, but not in the normal metal

    Populist Attitudes Predict Compliance-Related Attitudes and Behaviors During the COVID-19 Pandemic Via Trust in Institutions

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    While previous research discussed populism as a phenomenon of declining trust, we investigated the predictive value of populist attitudes for citizens’ trust, attitudes, and behaviors during the COVID-19 pandemic. Moreover, we tested the role of trust in several institutions simultaneously. As preregistered, the cross-sectional ( N = 1,090) and longitudinal ( n = 216) data collected (April to June, 2020) in Germany ( n = 617) and Poland ( n = 473) showed that stronger populist attitudes predicted higher trust in (a) alternative news media but less trust in (b) mainstream news media, (c) political institutions, and (d) scientific institutions. Moreover, we found negative effects of populist attitudes on acceptance and compliance, mediated via trust in political and scientific institutions (but not news media)

    Ethics education in pediatrics: Implementation and evaluation of an interactive online course for medical students

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    Introduction: The COVID-19 pandemic has catalyzed the development of online learning formats in virtually all areas of medical education. In pediatric ethics, online learning may not only substitute but also offer specific advantages over traditional classroom teaching. Many pediatricians rate their ethics education as poor and medical ethics education lacks evaluation, especially regarding the students’ needs. The aim of this project was to implement and evaluate a novel interactive distance learning approach to engage medical students in pediatric ethics education. Methods: An online ethics course was designed and delivered between May and June 2020. Core item of this course was a moderated, written forum discussion spanning several days. Evaluation was mixed methods. We evaluated the effectiveness of the course in terms of quality of the learning environment with a particular focus on relevance to students as well as interactive learning and reflective thinking. The Constructivist On-Line Learning Environment Survey (COLLES) was used to evaluate six different domains of the course. Data are presented as mean (standard deviation [SD]). The respective score range is 1-5, whereby a score of 4 or 5 means that the participants indicated the corresponding item as frequently or almost always present. Results: Responses were available from 104 (78.3%) of the 133 participating students. “Relevance” yielded a score of 4.17 (0.83), “reflective thinking” a score of 4.22 (0.83). “Interactivity” was scored 3.76 (0.99) and “tutor support” 4.72 (0.53). “Peer support” and “interpretation” scored 3.87 (0.98) and 4.49 (0.60), respectively. In qualitative analysis, students particularly valued the structure of the course, the relevance for their professional practice, their active participation and the incentive to reflective thinking. Students also indicated that this was an innovative and exciting format, which fills a current educational gap and should hence be continued beyond the pandemic. Conclusion: In conclusion, students actively engaged in online learning and perceived this ethics course as highly relevant for their professional practice

    Determination of sinapine in rapeseed pomace extract: its antioxidant and acetylcholinesterase inhibition properties.

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    Sinapine is the main secondary metabolite present in rapeseed pomace (RSP) with its concentration being dependent on rapeseed processing, growing conditions, extraction parameters and the country of origin. Here we report, the concentration of sinapine from an extract of defatted RSP harvested in the North East of Scotland. Using liquid chromatography tandem mass spectrometry, the most abundant phenolic compound in the RSP extract was, as expected, sinapine (109.1 mg/g RSP extract). Additionally, sinapic, caffeic, ferulic and syringic acids were identified (0.159-3.91 mg/g RSP extract). Sinapine together with the phenolics at the concentration present in the RSP extract, exhibited ≥ 50% activity relative to the extract in antioxidant assays. Furthermore, sinapine provided plasmid DNA (pBR322) protection, from 2,2'-azobis(2-amidinopropane) dihydrochloride and inhibited acetylcholinesterase activity by 85 %. Molecular docking was utilised to explain the inhibitory activity. RSP can be an excellent source of bioactive compounds for pharmaceuticals, food additive and nutraceutical applications

    A metabolomics approach to reveal the mechanism of developmental toxicity in zebrafish embryos exposed to 6-propyl-2-thiouracil

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    A crucial component of a substance registration and regulation is the evaluation of human prenatal developmental toxicity. Current toxicological tests are based on mammalian models, but these are costly, time consuming and may pose ethical concerns. The zebrafish embryo has evolved as a promising alternative model to study developmental toxicity. However, the implementation of the zebrafish embryotoxicity test is challenged by lacking information on the relevance of observed morphological alterations in fish for human developmental toxicity. Elucidating the mechanism of toxicity could help to overcome this limitation. Through LC-MS/MS and GC-MS metabolomics, we investigated whether changes to the endogenous metabolites can indicate pathways associated with developmental toxicity. To this aim, zebrafish embryos were exposed to different concentrations of 6-propyl-2-thiouracil (PTU), a compound known to induce developmental toxicity. The reproducibility and the concentration-dependence of the metabolome response and its association with morphological alterations were studied. Major morphological findings were reduced eye size, and other craniofacial anomalies; major metabolic changes included increased tyrosine, pipecolic acid and lysophosphatidylcholine levels, decreased methionine levels, and disturbance of the ‘Phenylalanine, tyrosine and tryptophan biosynthesis’ pathway. This pathway, and the changes in tyrosine and pipecolic acid levels could be linked to the mode of action of PTU, i.e., inhibition of thyroid peroxidase (TPO). The other findings suggested neurodevelopmental impairments. This proof-of-concept study demonstrated that metabolite changes in zebrafish embryos are robust and provide mechanistic information associated with the mode of action of PTU
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