Glutathione (GSH) is a tripeptide, which has many biological roles including protection against reactive oxygen and nitrogen species. The primary goal of this paper is to characterize the principal mechanisms of the protective role of GSH against reactive species and electrophiles. The ancillary goals are to provide up-to-date knowledge of GSH biosynthesis, hydrolysis, and utilization; intracellular compartmentalization and interorgan transfer; elimination of endogenously produced toxicants; involvement in metal homeostasis; glutathione-related enzymes and their regulation; glutathionylation of sulfhydryls. Individual sections are devoted to the relationships between GSH homeostasis and pathologies as well as to developed research tools and pharmacological approaches to manipulating GSH levels. Special attention is paid to compounds mainly of a natural origin (phytochemicals) which affect GSH-related processes. The paper provides starting points for development of novel tools and provides a hypothesis for investigation of the physiology and biochemistry of glutathione with a focus on human and animal health.

https://downloads.hindawi.com/archive/2012/736837.pdf

Glutathione Homeostasis and Functions: Potential Targets forMedical Interventions

Rapid advancements in stretchable and multifunctional electronics impose the challenge on corresponding power devices that they should have comparable stretchability and functionality We report a soft skin-like triboelectric nanogenerator (STENG) that enables both biomechanical energy harvesting and tactile sensing by hybridizing elastomer and ionic hydrogel as the electrification layer and electrode, respectively For the first time, ultrahigh stretchability (uniaxial strain, 1160%) and transparency (average transmittance, 962% for visible light) are achieved simultaneously for an energy-harvesting device The soft TENG is capable of outputting alternative electricity with an instantaneous peak power density of 35 mW m −2 and driving wearable electronics (for example, an electronic watch) with energy converted from human motions, whereas the STENG is pressure-sensitive, enabling its application as artificial electronic skin for touch/pressure perception Our work provides new opportunities for multifunctional power sources and potential applications in soft/wearable electronics

Ultrastretchable, transparent triboelectric nanogenerator as electronic skin for biomechanical energy harvesting and tactile sensing

In the past two decades, artificial skin-like materials have received increasing research interests for their broad applications in artificial intelligence, wearable devices, and soft robotics. However, profound challenges remain in terms of imitating human skin because of its unique combination of mechanical and sensory properties. In this work, a bioinspired mineral hydrogel is developed to fabricate a novel type of mechanically adaptable ionic skin sensor. Due to its unique viscoelastic properties, the hydrogel-based capacitive sensor is compliant, self-healable, and can sense subtle pressure changes, such as a gentle finger touch, human motion, or even small water droplets. It might not only show great potential in applications such as artificial intelligence, human/machine interactions, personal healthcare, and wearable devices, but also promote the development of next-generation mechanically adaptable intelligent skin-like devices.

A Bioinspired Mineral Hydrogel as a Self-Healable, Mechanically Adaptable Ionic Skin for Highly Sensitive Pressure Sensing.

A wide array of dietary phytochemicals have been reported to induce the expression of enzymes involved in both cellular antioxidant defenses and elimination/inactivation of electrophilic carcinogens. Induction of such cytoprotective enzymes by edible phytochemicals largely accounts for their cancer chemopreventive and chemoprotective activities. Nuclear factor-erythroid-2-related factor 2 (Nrf2) plays a crucial role in the coordinated induction of those genes encoding many stress-responsive and cytoptotective enzymes and related proteins. These include NAD(P)H:quinone oxidoreductase-1, heme oxygenase-1, glutamate cysteine ligase, glutathione S-transferase, glutathione peroxidase, thioredoxin, etc. In resting cells, Nrf2 is sequestered in the cytoplasm as an inactive complex with the repressor Kelch-like ECH-associated protein 1 (Keap1). The release of Nrf2 from its repressor is most likely to be achieved by alterations in the structure of Keap1. Keap1 contains several reactive cysteine residues that function as sensors of cellular redox changes. Oxidation or covalent modification of some of these critical cysteine thiols would stabilize Nrf2, thereby facilitating nuclear accumulation of Nrf2. After translocation into nucleus, Nrf2 forms a heterodimer with other transcription factors, such as small Maf, which in turn binds to the 5'-upstream CIS-acting regulatory sequence, termed antioxidant response elements (ARE) or electrophile response elements (EpRE), located in the promoter region of genes encoding various antioxidant and phase 2 detoxifying enzymes. Certain dietary chemopreventive agents target Keap1 by oxidizing or chemically modifying one or more of its specific cysteine thiols, thereby stabilizing Nrf2. In addition, phosphorylation of specific serine or threonine residues present in Nrf2 by upstream kinases may also facilitate the nuclear localization of Nrf2. Multiple mechanisms of Nrf2 activation by signals mediated by one or more of the upstream kinases, such as mitogen-activated protein kinases, phosphatidylionositol-3-kinase/Akt, protein kinase C, and casein kinase-2 have recently been proposed. This review highlights the cytoprotective gene expression induced by some representative dietary chemopreventive phytochemicals with the Nrf2-Keap1 system as a prime molecular target.

/pdf/nrf2-as-a-master-redox-switch-in-turning-on-the-cellular-2toecaelfk.pdf

Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals.

Regulation of Nrf2—an update

Because human-computer interactions are increasingly important, touch panels may require stretchability and biocompatibility in order to allow integration with the human body. However, most touch panels have been developed based on stiff and brittle electrodes. We demonstrate an ionic touch panel based on a polyacrylamide hydrogel containing lithium chloride salts. The panel is soft and stretchable, so it can sustain a large deformation. The panel can freely transmit light information because the hydrogel is transparent, with 98% transmittance for visible light. A surface-capacitive touch system was adopted to sense a touched position. The panel can be operated under more than 1000% areal strain without sacrificing its functionalities. Epidermal touch panel use on skin was demonstrated by writing words, playing a piano, and playing games.

http://science.sciencemag.org/content/sci/353/6300/682.full.pdf

Highly stretchable, transparent ionic touch panel

(-)-Epigallocatechin gallate induces Nrf2-mediated antioxidant enzyme expression via activation of PI3K and ERK in human mammary epithelial cells.

Piceatannol induces heme oxygenase-1 expression in human mammary epithelial cells through activation of ARE-driven Nrf2 signaling

Piceatannol (3,4,3\#8217;,5\#8217;-tetrahydroxy-trans-stilbene), derived from the seeds of Euphorbia lagascae, has been reported to have anti-proliferative, anti-inflammatory, and anti-oxidant properties. However, the mechanisms underlying its chemoprotective effects remain largely unresolved. In the present study, we found that piceatannol treatment (30 \#956;M) significantly upregulated the expression of the antioxidant enzyme heme oxygenase-1 (HO-1) and its mRNA transcript at 6 h and 3 h, respectively in human breast epithelial (MCF10A) cells. A redox-sensitive transcription factor NF-E2-related factor (Nrf2) plays a pivotal role in induced expression of many antioxidant and phase-2 detoxifying enzymes. Piceatannol induced translocation of Nrf2 into the nucleus and its transcriptional activities when treated to the MCF10A cells for 6 h. Up-regulation of HO-1 expression by piceatannol through direct binding of Nrf2 to antioxidant response element (ARE) was verified by the chromatin immunoprecipitation (ChIP) assay. siRNA knock down of Nrf2 gene abolished piceatannol-induced HO-1 expression. In addition, piceatannol-induced activation of Nrf2 was abrogated by the pharmacological inhibitor (LY294002) as well as the kinase dead form of Akt. HO-1 upregulation and Nrf2 activation induced by piceatannol were more prominent than those afforded by the same concentration of resveratrol (3,4\#8217;,5-trihydroxy-trans-stilbene) and oxyresveratrol (2,\#8217;,4,5\#8217;-tetrahydroxy-trans-stilbene), stilbene analogs structurally related to piceatannol. In an attempt to explain the cytoprotective or chemoprotective activity exerted by piceatannol, we examined its effect on the expression of HO-1 and the signaling pathways responsible for induction of this antioxidant enzyme. We hypothesize that an electrophilic quinone formed as a consequence of oxidation of piceatannol bearing the catechol moiety may bind covalently to Kelch-like ECH-associated protein 1 (Keap1), an inhibitory protein that sequesters Nrf2 in the cytoplasm. This will diminish the affinity of Keap1 for Nrf2. The thiol reducing agent dithiothreitol (100 \#956;M) attenuated piceatannol-induced Nrf2 activation and HO-1 expression. It is hence likely that piceatannol modifies specific cysteine residues of Keap1, which allows Nrf2 to translocate into the nucleus and bind to ARE, leading to enhancement of the expression of HO-1. The characteristic catechol moiety of piceatannol appears to be critical for the induction of Nrf2 activation and subsequent upregulation of HO-1. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 16.

Abstract #16: Piceatannol induces heme oxygenase-1 expression in human mammary epithelial cells through activation of ARE-driven Nrf2 signaling

Cross-linked highly sulfonated poly(arylene ether sulfone) membranes prepared by in-situ casting and thiol-ene click reaction for fuel cell application

Hyunhee Lee

Papers

Highly stretchable, transparent ionic touch panel

(-)-Epigallocatechin gallate induces Nrf2-mediated antioxidant enzyme expression via activation of PI3K and ERK in human mammary epithelial cells.

Piceatannol induces heme oxygenase-1 expression in human mammary epithelial cells through activation of ARE-driven Nrf2 signaling

Abstract #16: Piceatannol induces heme oxygenase-1 expression in human mammary epithelial cells through activation of ARE-driven Nrf2 signaling

Cross-linked highly sulfonated poly(arylene ether sulfone) membranes prepared by in-situ casting and thiol-ene click reaction for fuel cell application