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Sulforaphane targets cancer stemness and tumor initiating properties in oral squamous cell carcinomas via miR-200c induction
No full textAbstractBackground/PurposeCancer stem cells (CSCs) are deemed as the driving force of tumorigenesis in oral squamous cell carcinomas (OSCCs). In this study, we investigated the chemotherapeutic effect of sulforaphane, a dietary component from broccoli sprouts, on targeting OSCC-CSCs.MethodsThe effect of sulforaphane on normal oral epithelial cells (SG) and sphere-forming OSCC-CSCs isolated from SAS and GNM cells was examined. ALDH1 activity and CD44 positivity of OSCC-CSCs with sulforaphane treatment was assessed by flow cytometry analysis. In vitro and in vivo tumorigenicity assays of OSCC-CSCs with sulforaphane treatment were presented.ResultsWe observed that the sulforaphane dose-dependently eliminated the proliferation rate of OSCC-CSCs, whereas the inhibition on SG cells proliferation was limited. Cancer stemness properties including self-renewal, CD44 positivity, and ALDH1 activity were also decreased in OSCC-CSCs with different doses of sulforaphane treatment. Moreover, sulforaphane treatment of OSCC-CSCs decreased the migration, invasion, clonogenicity, and in vivo tumorigenicity of xenograghts. Sulforaphane treatment resulted in a dose-dependent increase in the levels of tumor suppressive miR200c.ConclusionThese lines of evidence suggest that sulforaphane can suppress the cancer stemness and tumor-initiating properties in OSCC-CSCs both in vitro and in vivo
Comparative performance of five Mexican plancha-type cookstoves using water boiling tests
No full textAbstractWhile plancha-type cookstoves are very popular and widely disseminated in Latin America, few peer review articles exist documenting their detailed technical performance. In this paper we use the standard Water Boiling Tests (WBT) to assess the energy and emission performance of five plancha-type cookstoves disseminated in about 450 thousand Mexican rural homes compared to the traditional 3-stone fire (TSF). In the high-power phase, average modified combustion efficiencies (MCE) for plancha-type stoves were 97±1% which was higher than TSF 93±4%, and reductions in CO and PM2.5 total emissions were on average 44%. Time to boil and specific fuel consumption, however, were increased in plancha-type stoves compared to the open fire as a result of the reduced overall thermal efficiency of the plancha during WBT. In the simmering phase, plancha-type stoves showed much more consistent performance reductions compared to the TSF. MCE for plancha stoves were on average 98±1% and 95±3% for the TSF, while reductions in CO and PM2.5 total emissions were on average 55%. In this phase 27% average savings in fuel use are achieved by plancha-type stoves. Removal of the plancha rings resulted in savings of specific fuel consumption (SFC), thermal efficiency (TE), and time to boil; however, CO and PM2.5 emissions increased significantly as flue air is drawn through the comal surface rather than through the combustion zone, resulting in suboptimal combustion conditions.International Workshop Agreement (IWA) energy performance Tiers for plancha-type stoves ranged from 0 to 1. However, these results contrast sharply with the well documented reductions in fuel consumption during daily cooking activities achieved by these stoves. IWA indoor emissions Tiers are 4 for both PM2.5 and CO using locally measured values for fugitive emissions. Optimization of combustion chamber design on these stoves in Mexico is desirable to further reduce indoor emissions and to reduce the impacts of neighborhood pollution that can re-infiltrate kitchens. Comparison of performance between plancha-type stoves and unvented stoves should reflect the substantial gains that are made by reducing indoor air pollution and exposures by venting pollutants
Fat and fibre interfere with the dramatic effect that nanoemulsified d-limonene has on the heat resistance of Listeria monocytogenes
No full textAbstractThe application of d-limonene in form of nanoemulsion has been proved to reduce dramatically the thermal resistance of Listeria monocytogenes in culture media. The present research shows very promising results on the application in food products. The thermal resistance of L. monocytogenes was reduced 90 times when 0.5 mM nanoemulsified d-limonene was added to apple juice. This is the biggest reduction in the heat resistance of a microorganism caused by an antimicrobial described ever. However, no effect was found in carrot juice. A carrot juice system was prepared in an attempt to unravel which juice constituents were responsible for the lack of effect. When fat and fibre were not included in the carrot juice system formulation, the thermal resistance of L. monocytogenes was, again, dramatically reduced in presence of nanoemulsified d-limonene, so these components were shown to interfere with the effect. Once this interaction with food constituents becomes solved, the addition of nanoemulsified antimicrobials would allow to reduce greatly the intensity of the thermal treatments currently applied in the food processing industry
Synthesis, characterization and pharmacological evaluation of (Z)-2-(5-(biphenyl-4-yl)-3-(1-(imino)ethyl)-2,3-dihydro-1,3,4-oxadiazol-2-yl)phenol derivatives as potent antimicrobial and antioxidant agents
No full textAbstractThe oxadiazole pharmacophore is considered a viable lead structure for the synthesis of more efficacious and broad spectrum antimicrobial agents. The significance of this study was to prepare various oxadiazole derivatives by introducing the 1,3,4 oxadiazole core into several molecules to explore the possibilities of some altered biological activities. Therefore, the study presents the synthesis, antimicrobial and antioxidant evaluation of a series of 1,3,4 substituted oxadiazole derivatives. Antimicrobial evaluation revealed that eighteen compounds were able to display variable growth inhibitory effects on the tested Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus, Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli and fungal strains Candida albicans and Aspergillus niger. Among the synthesized derivative analogues 6f, 6l and 6r were found to be the most effective antibacterial agents. While the compounds 6c, 6l and 6q were found to be the most promising antifungal agents. On the other hand, all the synthesized compounds 6a–6r were subjected to antioxidant activity but only analogues 6l and 6q were found to exhibit potent antioxidant activity. Further compound 6l containing p-nitro phenyl moiety along with oxadiazole pharmacophore proved to be the most active antimicrobial and antioxidant agent
The arduous quest for translating health care productivity gains into cost savings. Lessons from their evolution at economic scoring agencies in the Netherlands and the US
No full textAbstractWe analyze the assessments of recent health reforms by the Congressional Budget Office (CBO) in the United States and the Bureau for Economic Policy Analysis (CPB) in the Netherlands.Both reforms aim to capitalize on productivity gains, which is appealing for policymakers because of the potential for cost savings while maintaining – or enhancing – quality and access. These measures however generally translate into more health care, rather than care that is affordable and appropriate. Scoring agencies therefore have rightfully been reluctant to assign significant savings to these measures.Thus with regard to cost savings, both agencies instead have favored more traditional policy measures in the past. They are however increasingly mapping out loose ends and dilemmas for payers, including information asymmetries, reputation issues and provider business models that contradict the goals of policymakers. This calls for further exploring this avenue and the development of more integrated agendas that might commit actors and the spread of best practices
Optimization of a method based on micro-matrix solid-phase dispersion (micro-MSPD) for the determination of PCBs in mussel samples
No full textAbstractThis paper reports the development and optimization of micro-matrix solid-phase dispersion (micro-MSPD) of nine polychlorinated biphenyls (PCBs) in mussel samples (Mytilus galloprovincialis) by using a two-level factorial design. Four variables (amount of sample, anhydrous sodium sulphate, Florisil and solvent volume) were considered as factors in the optimization process. The results suggested that only the interaction between the amount of anhydrous sodium sulphate and the solvent volume was statistically significant for the overall recovery of a trichlorinated compound, CB 28. Generally most of the considered species exhibited a similar behaviour, the sample and Florisil amounts had a positive effect on PCBs extractions and solvent volume and sulphate amount had a negative effect. The analytical determination and confirmation of PCBs were carried out by using GC-ECD and GC-MS/MS, respectively. The method was validated having satisfactory precision and accuracy with RSD values below 6% and recoveries between 81 and 116% for all congeners. The optimized method was applied to the extraction of real mussel samples from two Galician Rías
Native structure of a retroviral envelope protein and its conformational change upon interaction with the target cell
No full textAbstractEnveloped viruses enter their host cells by membrane fusion. The process of attachment and fusion in retroviruses is mediated by a single viral envelope glycoprotein (Env). Conformational changes of Env in the course of fusion are a focus of intense studies. Here we provide further insight into the changes occurring in retroviral Env during its initial interaction with the cell, employing murine leukemia virus (MLV) as model system. We first determined the structure of both natively membrane anchored MLV Env and MLV Env tagged with YFP in the proline rich region (PRR) by electron cryo tomography (cET) and sub-volume averaging. At a resolution of ∼20Å, native MLV Env presents as a hollow trimer (height ∼85Å, diameter ∼120Å) composed of step-shaped protomers. The major difference to the YFP-tagged protein was in regions outside of the central trimer. Next, we focused on elucidating the changes in MLV Env upon interaction with a host cell. Virus interaction with the plasma membrane occurred over a large surface and Env clustering on the binding site was observed. Sub-volume averaging did yield a low-resolution structure of Env interacting with the cell, which had lost its threefold symmetry and was elongated by ∼35Å in comparison to the unbound protein. This indicates a major rearrangement of Env upon host cell binding. At the site of virus interaction, the otherwise clearly defined bilayer structure of the host cell plasma membrane was much less evident, indicative of integral membrane protein accumulation and/or a change in membrane lipid composition
Maternal BCG scar is associated with increased infant proinflammatory immune responses
No full textAbstractIntroductionPrenatal exposures such as infections and immunisation may influence infant responses. We had an opportunity to undertake an analysis of innate responses in infants within the context of a study investigating the effects of maternal mycobacterial exposures and infection on BCG vaccine-induced responses in Ugandan infants.Material and methodsMaternal and cord blood samples from 29 mother-infant pairs were stimulated with innate stimuli for 24h and cytokines and chemokines in supernatants were measured using the Luminex® assay. The associations between maternal latent Mycobacterium tuberculosis infection (LTBI), maternal BCG scar (adjusted for each other’s effect) and infant responses were examined using linear regression. Principal Component Analysis (PCA) was used to assess patterns of cytokine and chemokine responses. Gene expression profiles for pathways associated with maternal LTBI and with maternal BCG scar were examined using samples collected at one (n=42) and six (n=51) weeks after BCG immunisation using microarray.ResultsMaternal LTBI was positively associated with infant IP-10 responses with an adjusted geometric mean ratio (aGMR) [95% confidence interval (CI)] of 5.10 [1.21, 21.48]. Maternal BCG scar showed strong and consistent associations with IFN-γ (aGMR 2.69 [1.15, 6.17]), IL-12p70 (1.95 [1.10, 3.55]), IL-10 (1.82 [1.07, 3.09]), VEGF (3.55 [1.07, 11.48]) and IP-10 (6.76 [1.17, 38.02]). Further assessment of the associations using PCA showed no differences for maternal LTBI, but maternal BCG scar was associated with higher scores for principal component (PC) 1 (median level of scores: 1.44 in scar-positive versus −0.94 in scar-negative, p=0.020) in the infants. PC1 represented a controlled proinflammatory response. Interferon and inflammation response pathways were up-regulated in infants of mothers with LTBI at six weeks, and in infants of mothers with a BCG scar at one and six weeks after BCG immunisation.ConclusionsMaternal BCG scar had a stronger association with infant responses than maternal LTBI, with an increased proinflammatory immune profile
Shared Socio-Economic Pathways of the Energy Sector – Quantifying the Narratives
No full textAbstractEnergy is crucial for supporting basic human needs, development and well-being. The future evolution of the scale and character of the energy system will be fundamentally shaped by socioeconomic conditions and drivers, available energy resources, technologies of energy supply and transformation, and end-use energy demand. However, because energy-related activities are significant sources of greenhouse gas (GHG) emissions and other environmental and social externalities, energy system development will also be influenced by social acceptance and strategic policy choices. All of these uncertainties have important implications for many aspects of economic and environmental sustainability, and climate change in particular. In the Shared-Socioeconomic Pathway (SSP) framework these uncertainties are structured into five narratives, arranged according to the challenges to climate change mitigation and adaptation. In this study we explore future energy sector developments across the five SSPs using Integrated Assessment Models (IAMs), and we also provide summary output and analysis for selected scenarios of global emissions mitigation policies. The mitigation challenge strongly corresponds with global baseline energy sector growth over the 21st century, which varies between 40% and 230% depending on final energy consumer behavior, technological improvements, resource availability and policies. The future baseline CO2-emission range is even larger, as the most energy-intensive SSP also incorporates a comparatively high share of carbon-intensive fossil fuels, and vice versa. Inter-regional disparities in the SSPs are consistent with the underlying socioeconomic assumptions; these differences are particularly strong in the SSPs with large adaptation challenges, which have little inter-regional convergence in long-term income and final energy demand levels. The scenarios presented do not include feedbacks of climate change on energy sector development. The energy sector SSPs with and without emissions mitigation policies are introduced and analyzed here in order to contribute to future research in climate sciences, mitigation analysis, and studies on impacts, adaptation and vulnerability