Optical Characteristics of Oxygen-doped ZnTe Thin Films Deposited by Magnetron SputteringMethod

Seon Pil Kim,Sang Woo Pak,Eun Kyu Kim 한국진공학회 2011 한국진공학회 학술발표회초록집 Vol.41 No.-

Oxidative Stress Increases Phosphorylation of IκB Kinase-α by Enhancing NF-κB-Inducing Kinase after Transient Focal Cerebral Ischemia

Song, Yun Seon,Kim, Min-Soo,Kim, Hyun-Ae,Jung, Bo-In,Yang, Jiwon,Narasimhan, Purnima,Kim, Gab Seok,Jung, Joo Eun,Park, Eun-Hee,Chan, Pak H SAGE Publications 2010 Journal of cerebral blood flow and metabolism Vol.30 No.7

<P> The IκB kinase (IKK) complex is a central component in the classic activation of the nuclear factor-κB (NF-κB) pathway. It has been reported to function in physiologic responses, including cell death and inflammation. We have shown that IKK is regulated by oxidative status after transient focal cerebral ischemia (tFCI) in mice. However, the mechanism by which oxidative stress influences IKKs after tFCI is largely unknown. Nuclear accumulation and phosphorylation of IKKα (pIKKα) were observed 1 h after 30 mins of tFCI in mice. In copper/zinc-superoxide dismutase knockout mice, levels of NF-κB-inducing kinase (NIK) (an upstream kinase of IKKα), pIKKα, and phosphorylation of histone H3 (pH3) on Ser10 were increased after tFCI and were higher than in wild-type mice. Immunohistochemistry showed nuclear accumulation and pIKKα in mouse brain endothelial cells after tFCI. Nuclear factor-κB-inducing kinase was increased, and it enhanced pH3 by inducing pIKKα after oxygen-glucose deprivation (OGD) in mouse brain endothelial cells. Both NIK and pH3 interactions with IKKα were confirmed by coimmunoprecipitation. Treatment with IKKα small interfering RNA significantly reduced cell death after OGD. These results suggest that augmentation of NIK, IKKα, and pH3 in response to oxidative stress is involved in cell death after cerebral ischemia (or stroke). </P>

Carbon monoxide releasing molecule-2 protects mice against acute kidney injury through inhibition of ER stress

Uddin, Md Jamal,Pak, Eun Seon,Ha, Hunjoo The Korean Society of Pharmacology 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.5

Acute kidney injury (AKI), which is defined as a rapid decline of renal function, becomes common and recently recognized to be closely intertwined with chronic kidney diseases. Current treatment for AKI is largely supportive, and endoplasmic reticulum (ER) stress has emerged as a novel mediator of AKI. Since carbon monoxide attenuates ER stress, the objective of the present study aimed to determine the protective effect of carbon monoxide releasing molecule-2 (CORM2) on AKI associated with ER stress. Kidney injury was induced after LPS (15 mg/kg) treatment at 12 to 24 h in C57BL/6J mice. Pretreatment of CORM2 (30 mg/kg) effectively prevented LPS-induced oxidative stress and inflammation during AKI in mice. CORM2 treatment also effectively inhibited LPS-induced ER stress in AKI mice. In order to confirm effect of CO on the pathophysiological role of tubular epithelial cells in AKI, we used mProx24 cells. Pretreatment of CORM2 attenuated LPS-induced ER stress, oxidative stress, and inflammation in mProx24 cells. These data suggest that CO therapy may prevent ER stress-mediated AKI.

Spatial reproducibility of complex fractionated atrial electrogram depending on the direction and configuration of bipolar electrodes: an <i>in-silico</i> modeling study

Jun-Seop Song,Young-Seon Lee,Minki Hwang,Jung-Kee Lee,Changyong Li,Boyoung Joung,Moon-Hyoung Lee,Eun Bo Shim,Hui-Nam Pak 대한생리학회-대한약리학회 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.5

Although 3D-complex fractionated atrial electrogram (CFAE) mapping is useful in radiofrequency catheter ablation for persistent atrial fibrillation (AF), the directions and configuration of the bipolar electrodes may affect the electrogram. This study aimed to compare the spatial reproducibility of CFAE by changing the catheter orientations and electrode distance in an<i> in -silico </i>left atrium (LA). We conducted this study by importing the heart CT image of a patient with AF into a 3D-homogeneous human LA model. Electrogram morphology, CFAE-cycle lengths (CLs) were compared for 16 different orientations of a virtual bipolar conventional catheter (conv-cath: size 3.5 mm, inter-electrode distance 4.75 mm). Additionally, the spatial correlations of CFAE-CLs and the percentage of consistent sites with CFAECL<120 ms were analyzed. The results from the conv-cath were compared with that obtained using a mini catheter (mini-cath: size 1 mm, inter-electrode distance 2.5mm). Depending on the catheter orientation, the electrogram morphology and CFAE-CLs varied (conv-cath: 11.5±0.7% variation, mini-cath: 7.1±1.2% variation), however the mini-cath produced less variation of CFAE-CL than conv-cath (p<0.001). There were moderate spatial correlations among CFAE-CL measured at 16 orientations (conv-cath: r=0.3055±0.2194 vs. mini-cath: 0.6074±0.0733, p<0.001). Additionally, the ratio of consistent CFAE sites was higher for mini catheter than conventional one (38.3±4.6% vs. 22.3±1.4%, p<0.05). Electrograms and CFAE distribution are affected by catheter orientation and electrode configuration in the<i> </i><i>in -silico</i> LA model. However, there was moderate spatial consistency of CFAE areas, and narrowly spaced bipolar catheters were less influenced by catheter direction than conventional catheters.

Pan-Src kinase inhibitor treatment attenuates diabetic kidney injury via inhibition of Fyn kinase-mediated endoplasmic reticulum stress

Dorotea Debra,Jiang Songling,Pak Eun Seon,Son Jung Beom,Choi Hwan Geun,Ahn Sung-Min,Ha Hunjoo 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Src family kinases (SFKs) have been implicated in the pathogenesis of kidney fibrosis. However, the specific mechanism by which SFKs contribute to the progression of diabetic kidney disease (DKD) remains unclear. Our preliminary transcriptome analysis suggested that SFK expression was increased in diabetic kidneys and that the expression of Fyn (a member of the SFKs), along with genes related to unfolded protein responses from the endoplasmic reticulum (ER) stress signaling pathway, was upregulated in the tubules of human diabetic kidneys. Thus, we examined whether SFK-induced ER stress is associated with DKD progression. Mouse proximal tubular (mProx24) cells were transfected with Fyn or Lyn siRNA and exposed to high glucose and palmitate (HG-Pal). Streptozotocin-induced diabetic rats were treated with KF-1607, a novel pan-Src kinase inhibitor (SKI) with low toxicity. The effect of KF-1607 was compared to that of losartan, a standard treatment for patients with DKD. Among the SFK family members, the Fyn and Lyn kinases were upregulated under diabetic stress. HG-Pal induced p70S6 kinase and JNK/CHOP signaling and promoted tubular injury. Fyn knockdown but not Lyn knockdown inhibited this detrimental signaling pathway. In addition, diabetic rats treated with KF-1607 showed improved kidney function and decreased ER stress, inflammation, and fibrosis compared with those treated with losartan. Collectively, these findings indicate that Fyn kinase is a specific member of the SFKs implicated in ER stress activation leading to proximal tubular injury in the diabetic milieu and that pan-SKI treatment attenuates kidney injury in diabetic rats. These data highlight Fyn kinase as a viable target for the development of therapeutic agents for DKD.

Human milk oligosaccharide, 2´-fucosyllactose, attenuates platelet activation in arterial thrombosis

Yeon-Ji Kim,Malk Eun Pak,Jangmi Yun,Chul Soo Shin,Jong-Won Yoon,Seon-min Jeon,Young-Ha Song,Kyungho Kim 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

The ingestion of supplemental human milk oligosaccharides (HMOs) is associated with a lower risk of inflammatory diseases and infections. However, whether HMOs play an important role in regulating platelet aggregation and thrombus formation remains unclear. The current study aimed to investigate the antiplatelet effect of HMOs. The antiplatelet effect of HMOs including platelet aggregation, granule secretion, calcium mobilization, and integrin activation was assessed. Moreover, its antithrombotic effect was evaluated using an in vivo mouse model of ferric chloride-induced arterial thrombus formation. The transection tail bleeding time was used to evaluate whether HMOs inhibited primary hemostasis. Among all HMOs, 2′-fucosyllactose (2′-FL) could significantly inhibit collagen-related peptide-induced platelet aggregation, granule secretion, thromboxane B2 generation, serotonin secretion, and intracellular calcium mobilization. Notably, the inhibitory effect of 2′-FL was associated with the inhibition of glycoprotein VI-mediated platelet signal transduction during cell activation. In accordance with antiplatelet activities, the oral administration of 2′-FL was effective in blocking ferric chloride-induced arterial thrombus formation in vivo without prolonging bleeding time. Studies using a mouse model of ischemia-/reperfusion-induced stroke revealed that treatment with 2′-FL reduced infarct volume in stroke. Hence, the therapeutic potential of 2′-FL supplementation may play a protective role against thrombotic diseases.

Carbon monoxide releasing molecule-2 protects mice against acute kidney injury through inhibition of ER stress

Md Jamal Uddin,Eun Seon Pak,Hunjoo Ha 대한생리학회-대한약리학회 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.5

Acute kidney injury (AKI), which is defined as a rapid decline of renal function, becomes common and recently recognized to be closely intertwined with chronic kidney diseases. Current treatment for AKI is largely supportive, and endoplasmic reticulum (ER) stress has emerged as a novel mediator of AKI. Since carbon monoxide attenuates ER stress, the objective of the present study aimed to determine the protective effect of carbon monoxide releasing molecule-2 (CORM2) on AKI associated with ER stress. Kidney injury was induced after LPS (15 mg/kg) treatment at 12 to 24 h in C57BL/6J mice. Pretreatment of CORM2 (30 mg/kg) effectively prevented LPS-induced oxidative stress and inflammation during AKI in mice. CORM2 treatment also effectively inhibited LPS-induced ER stress in AKI mice. In order to confirm effect of CO on the pathophysiological role of tubular epithelial cells in AKI, we used mProx24 cells. Pretreatment of CORM2 attenuated LPS-induced ER stress, oxidative stress, and inflammation in mProx24 cells. These data suggest that CO therapy may prevent ER stress-mediated AKI.

Fibrillation Number Based on Wavelength and Critical Mass in Patients Who Underwent Radiofrequency Catheter Ablation for Atrial Fibrillation

Hwang, Minki,Park, Junbeum,Lee, Young-Seon,Park, Jae Hyung,Choi, Sung Hwan,Shim, Eun Bo,Pak, Hui-Nam IEEE 2015 IEEE Transactions on Biomedical Engineering Vol.62 No.2

<P>The heart characteristic length, the inverse of conduction velocity (CV), and the inverse of the refractory period are known to determine vulnerability to cardiac fibrillation (fibrillation number, FibN) in in silico or ex vivo models. The purpose of this study was to validate the accuracy of FibN through in silico atrial modeling and to evaluate its clinical application in patients with atrial fibrillation (AF) who had undergone radiofrequency catheter ablation. We compared the maintenance duration of AF at various FibNAF values using in silico bidomain atrial modeling. Among 60 patients (72% male, 54 ± 13 years old, 82% with paroxysmal AF) who underwent circumferential pulmonary vein isolation (CPVI) for AF rhythm control, we examined the relationship between FibNAF and postprocedural AF inducibility or induction pacing cycle length (iPCL). Clinical FibNAF was calculated using left atrium (LA) dimension (echocardiogram), the inverse of CV, and the inverse of the atrial effective refractory periods measured at proximal and distal coronary sinus. In silico simulation found a positive correlation between AF maintenance duration and FibN<SUB>AF</SUB> (R = 0.90, p <; 0.001). After clinical CPVI, FibN<SUB>AF</SUB> (0.296 ± 0.038 versus 0.192 ± 0.028, p <; 0.001) was significantly higher in patients with postprocedural AF inducibility (n = 41) than in those without (n = 19). Among 41 patients with postprocedural AF inducibility, FibN<SUB>AF</SUB> (P = 0.935, p <; 0.001) had excellent correlations with induction pacing cycle length. FibN<SUB>AF</SUB>, based on LA mass and wavelength, correlates well with AF maintenance in computational modeling and clinical AF inducibility after CPVI.</P>

Fyn Kinase: A Potential Therapeutic Target in Acute Kidney Injury

( Md Jamal Uddin ),( Debra Dorotea ),( Eun Seon Pak ),( Hunjoo Ha ) 한국응용약물학회 2020 Biomolecules & Therapeutics(구 응용약물학회지) Vol.28 No.3

Acute kidney injury (AKI) is a common disease with a complex pathophysiology which significantly contributes to the development of chronic kidney disease and end stage kidney failure. Preventing AKI can consequently reduce mortality, morbidity, and healthcare burden. However, there are no effective drugs in use for either prevention or treatment of AKI. Developing therapeutic agents with pleiotropic effects covering multiple pathophysiological pathways are likely to be more effective in attenuating AKI. Fyn, a nonreceptor tyrosine kinase, has been acknowledged to integrate multiple injurious stimuli in the kidney. Limited studies have shown increased Fyn transcription level and activation under experimental AKI. Activated Fyn kinase propagates various downstream signaling pathways associated to the progression of AKI, such as oxidative stress, inflammation, endoplasmic reticulum stress, as well as autophagy dysfunction. The versatility of Fyn kinase in mediating various pathophysiological pathways suggests that its inhibition can be a potential strategy in attenuating AKI.

Spatial reproducibility of complex fractionated atrial electrogram depending on the direction and configuration of bipolar electrodes: an in-silico modeling study

Song, Jun-Seop,Lee, Young-Seon,Hwang, Minki,Lee, Jung-Kee,Li, Changyong,Joung, Boyoung,Lee, Moon-Hyoung,Shim, Eun Bo,Pak, Hui-Nam The Korean Society of Pharmacology 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.5

Although 3D-complex fractionated atrial electrogram (CFAE) mapping is useful in radiofrequency catheter ablation for persistent atrial fibrillation (AF), the directions and configuration of the bipolar electrodes may affect the electrogram. This study aimed to compare the spatial reproducibility of CFAE by changing the catheter orientations and electrode distance in an in -silico left atrium (LA). We conducted this study by importing the heart CT image of a patient with AF into a 3D-homogeneous human LA model. Electrogram morphology, CFAE-cycle lengths (CLs) were compared for 16 different orientations of a virtual bipolar conventional catheter (conv-cath: size 3.5 mm, inter-electrode distance 4.75 mm). Additionally, the spatial correlations of CFAE-CLs and the percentage of consistent sites with CFAE-CL<120 ms were analyzed. The results from the conv-cath were compared with that obtained using a mini catheter (mini-cath: size 1 mm, inter-electrode distance 2.5 mm). Depending on the catheter orientation, the electrogram morphology and CFAE-CLs varied (conv-cath: $11.5{\pm}0.7%$ variation, mini-cath: $7.1{\pm}1.2%$ variation), however the mini-cath produced less variation of CFAE-CL than conv-cath (p<0.001). There were moderate spatial correlations among CFAE-CL measured at 16 orientations (conv-cath: $r=0.3055{\pm}0.2194$ vs. mini-cath: $0.6074{\pm}0.0733$, p<0.001). Additionally, the ratio of consistent CFAE sites was higher for mini catheter than conventional one ($38.3{\pm}4.6%$ vs. $22.3{\pm}1.4%$, p<0.05). Electrograms and CFAE distribution are affected by catheter orientation and electrode configuration in the in-silico LA model. However, there was moderate spatial consistency of CFAE areas, and narrowly spaced bipolar catheters were less influenced by catheter direction than conventional catheters.