Jiyeon Kwak

Physical limits of pure superparamagnetic Fe3O4 nanoparticles for a local hyperthermia agent in nanomedicine

Magnetic and AC magnetically induced heating characteristics of Fe3O4 nanoparticles (IONs) with different mean diameters, d, systematically controlled from 4.2 to 22.5 nm were investigated to explore the physical relationship between magnetic phase and specific loss power (SLP) for hyperthermia agent applications. It was experimentally confirmed that the IONs had three magnetic phases and correspondingly different SLP characteristics depending on the particle sizes. Furthermore, it was demonstrated that pure superparamagnetic phase IONs (d < 9.8 nm) showed insufficient SLPs critically limiting for hyperthermia applications due to smaller AC hysteresis loss power (Neel relaxation loss power) originated from lower out-of-phase magnetic susceptibility.

Involvement of the Nrf2-proteasome pathway in the endoplasmic reticulum stress response in pancreatic β-cells.

The ubiquitin-proteasome system plays a central role in protein quality control through endoplasmic reticulum (ER)-associated degradation (ERAD) of unfolded and misfolded proteins. NF-E2-related factor 2 (Nrf2) is a transcription factor that controls the expression of an array of phase II detoxification and antioxidant genes. Nrf2 signaling has additionally been shown to upregulate the expression of the proteasome catalytic subunits in several cell types. Here, we investigated the role of Nrf2 in tunicamycin-induced ER stress using a murine insulinoma β-cell line, βTC-6. shRNA-mediated silencing of Nrf2 expression in βTC-6 cells significantly increased tunicamycin-induced cytotoxicity, elevated the expression of the pro-apoptotic ER stress marker Chop10, and inhibited tunicamycin-inducible expression of the proteasomal catalytic subunits Psmb5 and Psmb6. The effects of 3H-1,2-dithiole-3-thione (D3T), a small molecule Nrf2 activator, on ER stress were also examined in βTC-6 cells. D3T pretreatment reduced tunicamycin cytotoxicity and attenuated the tunicamycin-inducible Chop10 and protein kinase RNA-activated-like ER kinase (Perk). The protective effect of D3T was shown to be associated with increased ERAD. D3T increased the expression of Psmb5 and Psmb6 and elevated chymotrypsin-like peptidase activity; proteasome inhibitor treatment blocked D3T effects on tunicamycin cytotoxicity and ER stress marker changes. Similarly, silencing of Nrf2 abolished the protective effect of D3T against ER stress. These results indicate that the Nrf2 pathway contributes to the ER stress response in pancreatic β-cells by enhancing proteasome-mediated ERAD.

Thimerosal decreases TRPV1 activity by oxidation of extracellular sulfhydryl residues

TRPV1, a receptor for capsaicin, plays a key role in mediating thermal and inflammatory pain. Because the modulation of ion channels by the cellular redox state is a significant determinant of channel function, we investigated the effects of sulfhydryl modification on the activity of TRPV1. Thimerosal, which oxidizes sulfhydryls, blocked the capsaicin-activated inward current (I(cap)) in cultured sensory neurons, in a reversible and dose-dependent manner, which was prevented by the co-application of the reducing agent, dithiothreitol. Among the three cysteine residues of TRPV1 that are exposed to the extracellular space, the oxidation-induced effect of thimerosal on I(cap) was blocked only by a point mutation at Cys621. These results suggest that the modification of an extracellular thiol group can alter the activity of TRPV1. Consequently, we propose that such a modulation of the redox state might regulate the physiological activity of TRPV1.

Capsaicin Blocks the Hyperpolarization-Activated Inward Currents via TRPV1 in the Rat Dorsal Root Ganglion Neurons.

Capsaicin, the pungent ingredient in hot pepper, activates nociceptors to produce pain and inflammation. However, prolonged exposures of capsaicin will cause desensitization to nociceptive stimuli. Hyperpolarization-activated cation currents (Ih) contribute to the maintenance of the resting membrane potential and excitability of neurons. In the cultured dorsal root ganglion (DRG) neurons, we investigated mechanisms underlying capsaicin-mediated modulation of Ih using patch clamp recordings. Capsaicin (1 µM) inhibited Ih only in the capsaicin-sensitive neurons. The capsaicin-induced inhibition of Ih was prevented by preexposing the TRPV1 antagonist, capsazepine (CPZ). Capsaicin-induced inhibition of Ih was dose dependent (IC50= 0.68 µM) and partially abolished by intracellular BAPTA and cyclosporin A, specific calcineurin inhibitor. In summary, the inhibitory effects of capsaicin on Ih are mediated by activation of TRPV1 and Ca2+-triggered cellular responses. Analgesic effects of capsaicin have been thought to be related to desensitization of nociceptive neurons due to depletion of pain-related substances. In addition, capsaicin-induced inhibition of Ih is likely to be important in understanding the analgesic mechanism of capsaicin.

Piezoelectric poly(vinylidene fluoride trifluoroethylene) thin film-based power generators using paper substrates for wearable device applications

Solution-derived poly(vinylidene fluoride trifluoroethylene) (P(VDF-TrFE)) piezoelectric thin films on cellulose paper substrates were prepared as flexible power generators for wearable device applications. Optimization of appropriate annealing and cooling sequences of the co-polymer films resulted in the formation of dense and uniform microstructures exhibiting a well-developed β-phase. A maximum open-circuit voltage of 1.5 V was generated from the periodic bending and releasing of the paper power generator at approximately 1 Hz. To demonstrate the wearable applications, P(VDF-TrFE) piezoelectric film-based paper power generators were directly attached on the back of a human hand, and they generated a maximum output open-circuit voltage of 0.4 V at low bending frequencies of 0.25 Hz. Good open-circuit voltage performance at low frequencies makes P(VDF-TrFE) piezoelectric thin films on paper substrates a strong candidate for future self-powered wearable devices.

BiFeO3-doped (K0.5,Na0.5)(Mn0.005,Nb0.995)O3 ferroelectric thin film capacitors for high energy density storage applications

Environmentally benign lead-free ferroelectric (K0.5,Na0.5)(Mn0.005,Nb0.995)O3 (KNMN) thin film capacitors with a small concentration of a BiFeO3 (BF) dopant were prepared by a cost effective chemical solution deposition method for high energy density storage device applications. 6 mol. % BF-doped KNMN thin films showed very slim hysteresis loops with high maximum and near-zero remanent polarization values due to a phase transition from the orthorhombic structure to the pseudo-cubic structure. Increasing the electric field up to 2 MV/cm, the total energy storage density (Jtotal), the effective recoverable energy density (Jeff), and the energy conversion efficiency (η) of lead-free KNMN-BF thin film capacitors were 31.0 J/cm3, 28.0 J/cm3, and 90.3%, respectively. In addition, these thin film capacitors exhibited a fast discharge time of a few μs and a high temperature stability up to 200 °C, proving their strong potential for high energy density storage and conversion applications.

Enhancement of Cycling Performance by Li2O–Sn Anode for All-Solid-State Batteries

A solid-state half-cell structure with a Sn–Li2O composite (SLC) anode/LiPON/Li was prepared to improve upon the cycling stability at the second discharging cycle of the non-Li anode thin films for all-solid-state batteries. Based on the cycling behaviors of the all-solid half cell with SLC and pure Sn thin film electrodes at first and second discharging cycles, cycling stability at the initial charging–discharging cycle of the all-solid-state battery system was improved. The high retention value of SLC thin film electrodes with LiPON solid electrolyte might originate from (1) the structural stability of the SLC thin film, and (2) suppression of crack formation at the SLC surface owing to an increasing surface mechanical strength of the SLC thin film by the LiPON deposition on it. These results indicate that the SLC thin film has a high possibility as the stable solid anode material for use as an all-solid-state battery.

Long-lasting enhancement in the intrinsic excitability of deep dorsal horn neurons.

Abstract Intrinsic excitability (IE) can be defined as an output of action potentials from a given input signal. Changes to the IE of a neuron are an important aspect of the cellular plasticity that underlies learning and memory process. In this study, long‐term plastic change in IE of deep dorsal horn neurons (DHNs) was investigated. Associative spike pairing stimulation (PS) induced a long‐lasting increase in IE. Buffering intracellular calcium with BAPTA (10 mM) prevented the induction of a long‐lasting increase in IE. PS failed to induce a long‐lasting increase in IE in the presence of either D‐APV (50 μM) or cadmium chloride (100 μM). Apamin (100 nM) partially blocked the induction of a long‐lasting increase in IE. This intrinsic plasticity requires a rise in postsynaptic Ca2+ and NMDA receptor activation during the induction period, and this process might be mediated by the down‐regulation of small‐conductance calcium‐dependent potassium (SK) channels. In deep DHNs, PS induced excitatory postsynaptic potential (EPSP)‐spike (E‐S) potentiation, which increases the firing probability and the number of spikes, by consistent dorsal rootlet stimulation. Under bath application of bicuculline (10 μM) and strychnine (1 μM), PS induced E‐S potentiation and long‐lasting increases in IE. These results suggest that an increase in IE might underlie E‐S potentiation, while a reduction in inhibitory transmission does not contribute to E‐S potentiation and long‐lasting increases in IE. We conclude that PS enhances the IE of deep DHNs, which may play an important role in spinal processing of nociceptive information.

Development of Estimation Methods of Skin Oxidation and Evaluation of Anti-Oxidative Effects of Genistein in Topical Formulations

The objective of the present study was to establish the method of measurement of hydrogen peroxide and to estimate the anti-oxidative effect of genistein in the skin. UVB induced skin oxidation and anti-oxidative effect of genistein formulations were evaluated by determining levels of hydrogen peroxide. The mechanism involved in the determination of hydrogen peroxide is based on a color reaction between ferric ion (Fe3+) and xylenol orange, often called FOX assay and subsequent monitoring of absorbance values of the reactant at 540 nm. The reaction was to some extent pH-dependent and detection sensitivity was greatest at pH 1.75. Genistein liposomal gel demonstrated better anti-oxidative effect with regard to lowering hydrogen peroxide levels elevated by UVB irradiation compared to genistein-suspended gel. A linear relationship has been observed between anti-oxidative effect of genistein and drug deposition in the skin tissue. Genistein liposomal gel resulting in the localization of the drug in the deeper skin led to improved anti-oxidative effect compared to genistein gel. The suggested method for evaluation of oxidation of the skin can be used as a tool to screen effective anti-oxidative agents and their delivery systems acting on the skin.