Hyewon Park

Self-Powered Cardiac Pacemaker Enabled by Flexible Single Crystalline PMN-PT Piezoelectric Energy Harvester

A flexible single-crystalline PMN-PT piezoelectric energy harvester is demonstrated to achieve a self-powered artificial cardiac pacemaker. The energy-harvesting device generates a short-circuit current of 0.223 mA and an open-circuit voltage of 8.2 V, which are enough not only to meet the standard for charging commercial batteries but also for stimulating the heart without an external power source.

Comprehensive biocompatibility of nontoxic and high-output flexible energy harvester using lead-free piezoceramic thin film

Flexible piezoelectric energy harvesters have been regarded as an overarching candidate for achieving self-powered electronic systems for environmental sensors and biomedical devices using the self-sufficient electrical energy. In this research, we realize a flexible high-output and lead-free piezoelectric energy harvester by using the aerosol deposition method and the laser lift-off process. We also investigated the comprehensive biocompatibility of the lead-free piezoceramic device using ex-vivo ionic elusion and in vivo bioimplantation, as well as in vitro cell proliferation and histologic inspection. The fabricated LiNbO3-doped (K,Na)NbO3 (KNN) thin film-based flexible energy harvester exhibited an outstanding piezoresponse, and average output performance of an open-circuit voltage of ∼130 V and a short-circuit current of ∼1.3 μ A under normal bending and release deformation, which is the best record among previously reported flexible lead-free piezoelectric energy harvesters. Although both the KNN an...

Self-Powered Real-Time Arterial Pulse Monitoring Using Ultrathin Epidermal Piezoelectric Sensors

Continuous monitoring of an arterial pulse using a pressure sensor attached on the epidermis is an important technology for detecting the early onset of cardiovascular disease and assessing personal health status. Conventional pulse sensors have the capability of detecting human biosignals, but have significant drawbacks of power consumption issues that limit sustainable operation of wearable medical devices. Here, a self-powered piezoelectric pulse sensor is demonstrated to enable in vivo measurement of radial/carotid pulse signals in near-surface arteries. The inorganic piezoelectric sensor on an ultrathin plastic achieves conformal contact with the complex texture of the rugged skin, which allows to respond to the tiny pulse changes arising on the surface of epidermis. Experimental studies provide characteristics of the sensor with a sensitivity (≈0.018 kPa-1 ), response time (≈60 ms), and good mechanical stability. Wireless transmission of detected arterial pressure signals to a smart phone demonstrates the possibility of self-powered and real-time pulse monitoring system.

RAGE siRNA-mediated gene silencing provides cardioprotection against ventricular arrhythmias in acute ischemia and reperfusion.

Expression of receptor for advanced glycation end-products (RAGE) is suggested to play a crucial role in mediating cardiac ischemia/reperfusion (IR) injury, and the blockade of RAGE signaling has been considered as a potential therapeutic strategy for the treatment of IR-induced cardiac damage. In this study, we primarily investigated the effects of RAGE suppression particularly on IR-induced ventricular arrhythmia. To inhibit the IR-induced upregulation of RAGE, siRNA targeting RAGE (siRAGE) was delivered to myocardium by using deoxycholic acid-modified polyethylenimine (PEI-DA) as a non-viral gene carrier. The resultant PEI-DA/siRAGE nanocomplexes successfully silenced the expression of RAGE and attenuated the inflammation and apoptosis in the ischemic-reperfused myocardium. According to our results, the electrophysiological properties (e.g., action potential propagation, action potential duration, and conduction velocity), disrupted by IR injury, were restored to normal level and the induction of ventricular tachycardia was abolished by RAGE silencing. We further found that RAGE suppression led to the activation of Wnt signaling, followed by the expression of gap junction protein, connexin43. Thus it could be concluded that successful siRAGE delivery is protective against IR-induced ventricular arrhythmia.

CHIP-mediated degradation of transglutaminase 2 negatively regulates tumor growth and angiogenesis in renal cancer

The multifunctional enzyme transglutaminase 2 (TG2) primarily catalyzes cross-linking reactions of proteins via (γ-glutamyl) lysine bonds. Several recent findings indicate that altered regulation of intracellular TG2 levels affects renal cancer. Elevated TG2 expression is observed in renal cancer. However, the molecular mechanism underlying TG2 degradation is not completely understood. Carboxyl-terminus of Hsp70-interacting protein (CHIP) functions as an ubiquitin E3 ligase. Previous studies reveal that CHIP deficiency mice displayed a reduced life span with accelerated aging in kidney tissues. Here we show that CHIP promotes polyubiquitination of TG2 and its subsequent proteasomal degradation. In addition, TG2 upregulation contributes to enhanced kidney tumorigenesis. Furthermore, CHIP-mediated TG2 downregulation is critical for the suppression of kidney tumor growth and angiogenesis. Notably, our findings are further supported by decreased CHIP expression in human renal cancer tissues and renal cancer cells. The present work reveals that CHIP-mediated TG2 ubiquitination and proteasomal degradation represent a novel regulatory mechanism that controls intracellular TG2 levels. Alterations in this pathway result in TG2 hyperexpression and consequently contribute to renal cancer.

Primary cardiac T cell lymphoma in a child.

Primary cardiac lymphoma (PCL) is a rare malignancy, defined as a non-Hodgkin s lymphoma involving only the heart and/or pericardium or as a lymphoma with the bulk of tumor located on the heart. Most of the cases develop in adults, and the tumors are predominantly of B cell origin [3]. Only a few cases of PCL have been described in children [1, 4, 5], and tumors of T cell origin have been presented in limited cases [2]. A 10-year-old boy presented with rapidly progressing respiratory difficulty for 2 days. On physical examination, the neck veins were engorged and bilateral lower extremity pitting edema was observed. On the echocardiogram, a huge homogeneous echogenic mass was observed in the right atrium, and the inflow through the tricuspid valve was disturbed by the tumor. The mass was confirmed on chest computed tomography (CT) and magnetic resonance imaging (Fig. 1), and these studies also revealed a lung mass in the left upper lobe. The tumor was surgically excised to relieve the right ventricular inflow obstruction and the pulmonary nodule was concomitantly resected. The pathologic examination and immunohistochemical staining of the specimen confirmed the diagnosis of ALK+ anaplastic large cell lymphoma of cytotoxic T cell lineage (Fig. 2). The lung mass had identical pathologic features. After the pathologic diagnosis was obtained, a bone marrow biopsy, whole body positron emission tomography scan, and bone scan were performed, but there was no evidence of tumor in other organs or lymph nodes. Postoperatively, chemotherapy with methotrexate, cytosine arabinoside, and hydrocortisone was started. CT scan revealed no evidence of residual tumor or tumor recurrence at 12-month follow-up (six cycles of chemotherapy). Although PCL is extremely rare in the pediatric population, it should not be excluded in the differential diagnosis for pediatric patients with a cardiac tumor. A favorable outcome can be achieved by early histologic diagnosis and precise evaluation of the disease followed by multimodality treatment.

The band offset measurement at the In0.5Ga0.5P/GaAs heterojunction by using properties of transition metal☆

Abstract It is well known that the energy level of a transition metal (TM) such as manganese is tied to the vacuum level rather than to a particular band extreme in semiconductors. Therefore, TM can be used as a common reference energy level in all the semiconductors. We have investigated for the first time the photoluminescence spectrum of Mn-doped In0.5Ga0.5P/GaAs heterojunction and by using the Mn acceptor level in photoluminescence (PL) spectra, the fractional band offsets Qc and Qv for the In0.5Ga0.5P/GaAs heterojunction are determined as 0.63 and 0.37, respectively.

Extracellular Vesicles Derived from Hypoxic Human Mesenchymal Stem Cells Attenuate GSK3β Expression via miRNA-26a in an Ischemia-Reperfusion Injury Model

Purpose Bioactive molecules critical to intracellular signaling are contained in extracellular vesicles (EVs) and have cardioprotective effects in ischemia/reperfusion (IR) injured hearts. This study investigated the mechanism of the cardioprotective effects of EVs derived from hypoxia-preconditioned human mesenchymal stem cells (MSCs). Materials and Methods EV solutions (0.4 µg/µL) derived from normoxia-preconditioned MSCs (EVNM) and hypoxia-preconditioned MSCs (EVHM) were delivered in a rat IR injury model. Successful EV delivery was confirmed by the detection of PKH26 staining in hearts from EV-treated rats. Results EVHM significantly reduced infarct size (24±2% vs. 8±1%, p<0.001), and diminished arrhythmias by recovering electrical conduction, INa current, and Cx43 expression. EVHM also reversed reductions in Wnt1 and β-catenin levels and increases in GSK3β induced after IR injury. miRNA-26a was significantly increased in EVHM, compared with EVNM, in real-time PCR. Finally, in in vitro experiments, hypoxia-induced increases in GSK3β expression were significantly reduced by the overexpression of miRNA-26a. Conclusion EVHM reduced IR injury by suppressing GSK3β expression via miRNA-26a and increased Cx43 expression. These findings suggest that the beneficial effect of EVHM is related with Wnt signaling pathway.

Programmed cell death 5 suppresses AKT-mediated cytoprotection of endothelium

Significance Programmed cell death 5 (PDCD5) plays a pivotal role in cellular apoptosis. Pathological relevance of PDCD5 is mostly found in human cancers; however, the role of PDCD5 in noncancerous diseases is not fully elucidated. Here we show that mice with endothelial PDCD5 deficiency have elevated serum nitric oxide levels and an atheroprotective effect in blood vessels. In addition, PDCD5 disrupts the HDAC3–protein kinase B (PKB/AKT) interaction and inhibits AKT-eNOS signaling and nitric oxide production in vivo and in vitro. Moreover, serum PDCD5 reflects vascular endothelial status, which is significantly correlated with cardiovascular risk. Our results demonstrate a mechanism of endothelial homeostasis and provide a potential therapeutic target for improving endothelial function. Programmed cell death 5 (PDCD5) has been associated with human cancers as a regulator of cell death; however, the role of PDCD5 in the endothelium has not been revealed. Thus, we investigated whether PDCD5 regulates protein kinase B (PKB/AKT)-endothelial nitric oxide synthase (eNOS)–dependent signal transduction in the endothelium and affects atherosclerosis. Endothelial-specific PDCD5 knockout mice showed significantly reduced vascular remodeling compared with wild-type (WT) mice after partial carotid ligation. WT PDCD5 competitively inhibited interaction between histone deacetylase 3 (HDAC3) and AKT, but PDCD5L6R, an HDAC3-binding–deficient mutant, did not. Knockdown of PDCD5 accelerated HDAC3–AKT interaction, AKT and eNOS phosphorylation, and nitric oxide (NO) production in human umbilical vein endothelial cells. Moreover, we found that serum PDCD5 levels reflect endothelial NO production and are correlated with diabetes mellitus, high-density lipoprotein cholesterol, and coronary calcium in human samples obtained from the cardiovascular high-risk cohort. Therefore, we conclude that PDCD5 is associated with endothelial dysfunction and may be a novel therapeutic target in atherosclerosis.

The Role of Serotonin in Ventricular Repolarization in Pregnant Mice

Purpose The mechanisms underlying repolarization abnormalities during pregnancy are not fully understood. Although maternal serotonin (5-hydroxytryptamine, 5-HT) production is an important determinant for normal fetal development in mice, its role in mothers remains unclear. We evaluated the role of serotonin in ventricular repolarization in mice hearts via 5Htr3 receptor (Htr3a) and investigated the mechanism of QT-prolongation during pregnancy. Materials and Methods We measured current amplitudes and the expression levels of voltage-gated K+ (Kv) channels in freshly-isolated left ventricular myocytes from wild-type non-pregnant (WT-NP), late-pregnant (WT-LP), and non-pregnant Htr3a homozygous knockout mice (Htr3a−/−-NP). Results During pregnancy, serotonin and tryptophan hydroxylase 1, a rate-limiting enzyme for the synthesis of serotonin, were markedly increased in hearts and serum. Serotonin increased Kv current densities concomitant with the shortening of the QT interval in WT-NP mice, but not in WT-LP and Htr3a−/−-NP mice. Ondansetron, an Htr3 antagonist, decreased Kv currents in WT-LP mice, but not in WT-NP mice. Kv4.3 directly interacted with Htr3a, and this binding was facilitated by serotonin. Serotonin increased the trafficking of Kv4.3 channels to the cellular membrane in WT-NP. Conclusion Serotonin increases repolarizing currents by augmenting Kv currents. Elevated serotonin levels during pregnancy counterbalance pregnancy-related QT prolongation by facilitating Htr3-mediated Kv currents.