Use of quercetin in animal feed : effects on the P-gp expression and pharmacokinetics of orally administrated enrofloxacin in chicken

Modulation of P-glycoprotein (P-gp, encoded by Mdr1) by xenobiotics plays central role in pharmacokinetics of various drugs. Quercetin has a potential to modulate P-gp in rodents, however, its effects on P-gp modulation in chicken are still unclear. Herein, study reports role of quercetin in modulation of P-gp expression and subsequent effects on the pharmacokinetics of enrofloxacin in broilers. Results show that P-gp expression was increased in a dose-dependent manner following exposure to quercetin in Caco-2 cells and tissues of chicken. Absorption rate constant and apparent permeability coefficient of rhodamine 123 were decreased, reflecting efflux function of P-gp in chicken intestine increased by quercetin. Quercetin altered pharmacokinetic of enrofloxacin by decreasing area under curve, peak concentration, and time to reach peak concentration and by increasing clearance rate. Molecular docking shows quercetin can form favorable interactions with binding pocket of chicken xenobiotic receptor (CXR). Results provide convincing evidence that quercetin induced P-gp expression in tissues by possible interaction with CXR, and consequently reducing bioavailability of orally administered enrofloxacin through restricting its intestinal absorption and liver/kidney clearance in broilers. The results can be further extended to guide reasonable use of quercetin to avoid drug-feed interaction occurred with co-administered enrofloxacin or other similar antimicrobials.Peer reviewedFinal Published versio

Prevalence and Predictors of Vitamin D Insufficiency in Children: A Great Britain Population Based Study

Objectives To evaluate the prevalence and predictors of vitamin D insufficiency (VDI) in children In Great Britain. Design A nationally representative cross-sectional study survey of children (1102) aged 4–18 years (999 white, 570 male) living in private households (January 1997–1998). Interventions provided information about dietary habits, physical activity, socio-demographics, and blood sample. Outcome measures were vitamin D insufficiency (<50 nmol/L). Results Vitamin D levels (mean = 62.1 nmol/L, 95%CI 60.4–63.7) were insufficient in 35%, and decreased with age in both sexes (p<0.001). Young People living between 53–59 degrees latitude had lower levels (compared with 50–53 degrees, p = 0.045). Dietary intake and gender had no effect on vitamin D status. A logistic regression model showed increased risk of VDI in the following: adolescents (14–18 years old), odds ratio (OR) = 3.6 (95%CI 1.8–7.2) compared with younger children (4–8 years); non white children (OR = 37 [95%CI 15–90]); blood levels taken December-May (OR = 6.5 [95%CI 4.3–10.1]); on income support (OR = 2.2 [95%CI 1.3–3.9]); not taking vitamin D supplementation (OR = 3.7 [95%CI 1.4–9.8]); being overweight (OR 1.6 [95%CI 1.0–2.5]); <1/2 hour outdoor exercise/day/week (OR = 1.5 [95%CI 1.0–2.3]); watched >2.5 hours of TV/day/week (OR = 1.6[95%CI 1.0–2.4]). Conclusion We confirm a previously under-recognised risk of VDI in adolescents. The marked higher risk for VDI in non-white children suggests they should be targeted in any preventative strategies. The association of higher risk of VDI among children who exercised less outdoors, watched more TV and were overweight highlights potentially modifiable risk factors. Clearer guidelines and an increased awareness especially in adolescents are needed, as there are no recommendations for vitamin D supplementation in older children

Self-driving Multimodal Studies at User Facilities

Multimodal characterization is commonly required for understanding materials. User facilities possess the infrastructure to perform these measurements, albeit in serial over days to months. In this paper, we describe a unified multimodal measurement of a single sample library at distant instruments, driven by a concert of distributed agents that use analysis from each modality to inform the direction of the other in real time. Powered by the Bluesky project at the National Synchrotron Light Source II, this experiment is a world's first for beamline science, and provides a blueprint for future approaches to multimodal and multifidelity experiments at user facilities.Comment: 36th Conference on Neural Information Processing Systems (NeurIPS 2022). AI4Mat Worksho

Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease

PMCID: PMC3710212This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Open Data, Open Source and Open Standards in chemistry: The Blue Obelisk five years on

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background The Blue Obelisk movement was established in 2005 as a response to the lack of Open Data, Open Standards and Open Source (ODOSOS) in chemistry. It aims to make it easier to carry out chemistry research by promoting interoperability between chemistry software, encouraging cooperation between Open Source developers, and developing community resources and Open Standards. Results This contribution looks back on the work carried out by the Blue Obelisk in the past 5 years and surveys progress and remaining challenges in the areas of Open Data, Open Standards, and Open Source in chemistry. Conclusions We show that the Blue Obelisk has been very successful in bringing together researchers and developers with common interests in ODOSOS, leading to development of many useful resources freely available to the chemistry community.Peer Reviewe

Excimer formation by steric twisting in carbazole and triphenylamine-based host materials

This paper presents a detailed spectroscopic investigation of luminescence properties of 4,4′-Bis(N-carbazolyl)-1,1′-biphenyl (CBP) and N,N,N’,N’-tetraphenylbenzidine (TAD) in solutions and neat films. These compounds are compared to their derivatives CDBP and TDAD that contain methyl groups in the 2 and 2’ position of the biphenyl core. We find that whereas steric twisting in CDBP and TDAD leads to a high triplet energy of about 3.0 and 3.1 eV, respectively, these compounds also tend to form triplet excimers in a neat film, in contrast to CBP and TAD. By comparison with N-phenylcarbazole (NPC) and triphenylamine (TPA), on which these compounds are based, as well as with the rigid spiro analogs to CBP and TAD we show that the reduced excimer formation in CBP and TAD can be attributed to a localization of the excitation onto the central biphenyl part of the molecule.We acknowledge support from the Federal Ministry of Education and Research (BMBF) through the project ‘Trip-Q’, the German Science Foundation (DFG) through the Research and Training Group GRK 1640 and the UK Engineering and Physical Sciences Research Council (grant number EP/G060738/1).This is the final published version. It first appeared at http://pubs.acs.org/doi/abs/10.1021/jp512772j

Influence of structural isomerism and fluorine atom substitution on the self-association of naphthoic acid

The self-association of small aromatic systems driven by π-π stacking and hydrophobic interactions is well known. Understanding the nature of these interactions is important if they are to be used to control association. Here, we present results of an NMR study into the self-association of two isomers of naphthoic acid along with an investigation into the role of a fluorine substituent on that self- association. We interpret the results in terms of a simple isodesmic model of self- association and show that the addition of the fluorine atom appears to increase the stability of the aggregates by an order of magnitude (e.g. 1-naphothic acid vs 4- fluoro-1-naphthoic acid Keq = 0.05 increases to 0.35 M-1), a result which is supported by computational studies in the literature on the role of substituent effects on interaction energy. The use of fluorinated isomers to probe the assembly is also presented, with differing trends in fluorine-19 chemical shifts observed depending on the isomer substitution pattern

Self-trapping of excitons, violation of condon approximation, and efficient fluorescence in conjugated cycloparaphenylenes

Cycloparaphenylenes, the simplest structural unit of armchair carbon nanotubes, have unique optoelectronic properties counterintuitive in the class of conjugated organic materials. Our time-dependent density functional theory study and excited state dynamics simulations of cycloparaphenylene chromophores provide a simple and conceptually appealing physical picture explaining experimentally observed trends in optical properties in this family of molecules. Fully delocalized degenerate second and third excitonic states define linear absorption spectra. Self-trapping of the lowest excitonic state due to electron-phonon coupling leads to the formation of spatially localized excitation in large cycloparaphenylenes within 100 fs. This invalidates the commonly used Condon approximation and breaks optical selection rules, making these materials superior fluorophores. This process does not occur in the small molecules, which remain inefficient emitters. A complex interplay of symmetry, π-conjugation, conformational distortion and bending strain controls all photophysics of cycloparaphenylenes.Fil: Adamska, Lyudmyla. Los Alamos National Laboratory. Los Alamos; Estados UnidosFil: Nayyar, Iffat. Los Alamos National Laboratory. Los Alamos; Estados UnidosFil: Chen, Hang. Boston University; Estados UnidosFil: Swan, Anna K.. Boston University; Estados UnidosFil: Oldani, Andres Nicolas. Universidad Nacional de Quilmes; ArgentinaFil: Fernández Alberti, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Golder, Matthew R.. University of Oregon; Estados UnidosFil: Jasti, Ramesh. University of Oregon; Estados UnidosFil: Doorn, Stephen K.. Los Alamos National Laboratory. Los Alamos; Estados UnidosFil: Tretiak, Sergei. Los Alamos National Laboratory. Los Alamos; Estados Unido

Argyrin B a non-competitive inhibitor of the human immunoproteasome exhibiting preference for β1i

Inhibitors of the proteasome have found broad therapeutic applications however, they show severe toxicity due to the abundance of proteasomes in healthy cells. In contrast, inhibitors of the immunoproteasome, which is upregulated during disease states, are less toxic and have increased therapeutic potential including against autoimmune disorders. In this project, we report argyrin B, a natural product cyclic peptide to be a reversible, non-competitive inhibitor of the immunoproteasome. Argyrin B showed selective inhibition of the β5i and β1i sites of the immunoproteasome over the β5c and β1c sites of the constitutive proteasome with nearly 20-fold selective inhibition of β1i over the homologous β1c. Molecular modelling attributes the β1i over β1c selectivity to the small hydrophobic S1 pocket of β1i and β5i over β5c to site-specific amino acid variations that enable additional bonding interactions and stabilization of the binding conformation. These findings facilitate the design of immunoproteasome selective and reversible inhibitors that may have a greater therapeutic potential and lower toxicity

A diarylamine derived from anthranilic acid inhibits ZIKV replication

Zika virus (ZIKV) is a mosquito-transmitted Flavivirus, originally identified in Uganda in 1947 and recently associated with a large outbreak in South America. Despite extensive efforts there are currently no approved antiviral compounds for treatment of ZIKV infection. Here we describe the antiviral activity of diarylamines derived from anthranilic acid (FAMs) against ZIKV. A synthetic FAM (E3) demonstrated anti-ZIKV potential by reducing viral replication up to 86%. We analyzed the possible mechanisms of action of FAM E3 by evaluating the intercalation of this compound into the viral dsRNA and its interaction with the RNA polymerase of bacteriophage SP6. However, FAM E3 did not act by these mechanisms. In silico results predicted that FAM E3 might bind to the ZIKV NS3 helicase suggesting that this protein could be one possible target of this compound. To test this, the thermal stability and the ATPase activity of the ZIKV NS3 helicase domain (NS3Hel) were investigated in vitro and we demonstrated that FAM E3 could indeed bind to and stabilize NS3Hel