natural mediator
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Author(s):  
Ciaran A Shaughnessy ◽  
Sangya Yadav ◽  
Preston E Bratcher ◽  
Pamela L Zeitlin

Cystic fibrosis (CF) is a genetic disease caused by mutations of the gene encoding a cAMP-activated Cl- channel, the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR modulator therapies consist of small-molecule drugs that rescue mutant CFTR. Regimens of single or combinations of CFTR modulators still rely on endogenous levels of cAMP to regulate CFTR activity. We investigated CFTR activation by the natural mediator prostaglandin E2 (PGE2) and lubiprostone and tested the hypothesis that receptor-mediated CFTR activators can be used in combination with currently available CFTR modulators to increase function of mutant CFTR. Primary cultured airway epithelia were assayed in Ussing chambers. Experimental CFTR activators and established CFTR modulators were applied for 24 h and/or acutely and analyzed for their effect on CFTR activity as measured by changes in short-circuit current (ISC). In non-CF airway epithelia, acute application of lubiprostone and PGE2 activated CFTR to levels comparable to forskolin. Pre-treatment (24 h) with antagonists to prostaglandin receptors EP2 and EP4 abolished the ability of lubiprostone to acutely activate CFTR. In F508del homozygous airway epithelia pre-treated with the triple combination of elexacaftor, tezacaftor, and ivacaftor (ELEXA/TEZ/IVA; i.e., Trikafta), acute application of lubiprostone was able to maximally activate CFTR. Prolonged (24 h) co-treatment of F508del homozygous epithelia with ELEXA/TEZ/IVA and lubiprostone increased acute CFTR activation by ~60% compared to treatment with ELEXA/TEZ/IVA alone. This work establishes the feasibility of targeting prostaglandin receptors to activate CFTR on the airway epithelia and demonstrates that co-treatment with lubiprostone can further restore modulator-rescued CFTR.


Polymers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 3671
Author(s):  
Saerom Park ◽  
Dahun Jung ◽  
Hyejin Do ◽  
Jonghyeon Yun ◽  
Dongjun Lee ◽  
...  

In this study, a laccase-mediator system (LMS) using a natural mediator was developed as a whitening agent for melanin decolorization. Seven natural mediators were used to replace synthetic mediators and successfully overcome the low redox potential of laccase and limited access of melanin to the active site of laccase. The melanin decolorization activity of laccases from Trametes versicolor (lacT) and Myceliophthora thermophila (lacM) was significantly enhanced using natural mediators including acetosyringone, syringaldehyde, and acetovanillone, which showed low cytotoxicity. The methoxy and ketone groups of natural mediators play an important role in melanin decolorization. The specificity constants of lacT and lacM for melanin decolorization were enhanced by 247 and 334, respectively, when acetosyringone was used as a mediator. LMS using lacM and acetosyringone could also decolorize the melanin present in the cellulose hydrogel film, which mimics the skin condition. Furthermore, LMS could decolorize not only synthetic eumelanin analogs prepared by the oxidation of tyrosine but also natural melanin produced by melanoma cells.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Kun Zhang ◽  
Yeying Wu ◽  
Juan Huang ◽  
Youxun Liu

The high cost, potential toxicity, and possible enzyme inhibition ability of artificial mediators have limited the large-scale application of laccase (Lac)/mediator systems. Here, sinapic acid (SA), a natural mediator, was covalently attached to amino-functionalized magnetic nanoparticles (MNPs) via amide bond formation. The as-prepared SA@MNPs were characterized by Fourier-transform infrared spectroscopy, scanning electron microscopy, cyclic voltammetry, and thermogravimetric analysis. The SA@MNPs were then applied to evaluate the activity of the immobilized mediator for Lac-catalyzed dye decolorization using indigo carmine (IC) as a model dye. When SA and SA@MNPs were used as Lac mediators, IC decolorization yields of ∼93% and 96%, respectively, were obtained after 60 min. Moreover, SA@MNPs exhibited an IC decolorization yield of ∼90% after being reused for 8 cycles. The Lac/SA@MNP system was shown to degrade IC by breaking down the chromophoric group. The easy recyclability, good reusability, nontoxicity, and relatively low cost of SA@MNPs make this immobilized natural mediator a promising tool for dye treatment.


2019 ◽  
Vol 22 ◽  
pp. 101420 ◽  
Author(s):  
Ismat Bibi ◽  
Shumaila Javed ◽  
Sadia Ata ◽  
Farzana Majid ◽  
Shagufta Kamal ◽  
...  

2019 ◽  
Vol 26 (5) ◽  
pp. 913-920 ◽  
Author(s):  
Alba Blánquez ◽  
Juana Rodríguez ◽  
Vânia Brissos ◽  
Sonia Mendes ◽  
Ligia O. Martins ◽  
...  

2018 ◽  
Vol 44 (2) ◽  
pp. 210-240 ◽  
Author(s):  
Tracy M. Sweet

There are some educational interventions aimed at changing the ways in which individuals interact, and social networks are particularly useful for quantifying these changes. For many of these interventions, the ultimate goal is to change some outcome of interest such as teacher quality or student achievement, and social networks act as a natural mediator; the intervention changes the social networks of the teachers in schools, and teachers with certain types of social networks tend to use better teaching practices, for example. Due to lack of methodology, however, social networks have not been modeled as mediators. We present a new framework for modeling social networks as mediators in which a social network model is embedded into a mediation model and both models are estimated simultaneously. As a proof of concept, we introduce a new network model for mediation, applicable for interventions that affect subgroup structure. We provide a small simulation study to demonstrate the feasibility of this model and explore some potential operating characteristics. Finally, we apply our model to examine the effects of instructional coaches on teacher advice-seeking networks and subsequent changes in beliefs about mathematics.


2017 ◽  
Vol 1 (7) ◽  
pp. 1573-1579 ◽  
Author(s):  
Bin Yao ◽  
Praveen Kolla ◽  
Ranjit Koodali ◽  
Selvaratn Balaranjan ◽  
Sunav Shrestha ◽  
...  

Being a major byproduct of pulp and paper industry, lignin has attracted attention as a source of high-value organic chemicals,e.g.phenolic monomers that can be produced by lignin enzymatic treatment.


2017 ◽  
Vol 41 (3) ◽  
pp. 958-964 ◽  
Author(s):  
Bin Yao ◽  
Praveen Kolla ◽  
Ranjit Koodali ◽  
Yichun Ding ◽  
Selvaratnam Balaranjan ◽  
...  

The electrochemical oxidation mechanism of alkali lignin in the presence of a laccase–mediator system (LMS) in an aerobic environment.


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