Publications by authors named "Su-Jeong Choi"

18 Publications

  • Page 1 of 1

Neural stem cells derived from human midbrain organoids as a stable source for treating Parkinson's disease: Midbrain organoid-NSCs (Og-NSC) as a stable source for PD treatment.

Prog Neurobiol 2021 May 28:102086. Epub 2021 May 28.

Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Republic of Korea; Hanyang Biomedical Research Institute, Hanyang University, Seoul, Republic of Korea; Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea. Electronic address:

Successful clinical translation of stem cell-based therapy largely relies on the scalable and reproducible preparation of donor cells with potent therapeutic capacities. In this study, midbrain organoids were yielded from human pluripotent stem cells (hPSCs) to prepare cells for Parkinson's disease (PD) therapy. Neural stem/precursor cells (NSCs) isolated from midbrain organoids (Og-NSCs) expanded stably and differentiated into midbrain-type dopamine(mDA) neurons, and an unprecedentedly high proportion expressed midbrain-specific factors, with relatively low cell line and batch-to-batch variations. Single cell transcriptome analysis followed by in vitro assays indicated that the majority of cells in the Og-NSC cultures are ventral midbrain (VM)-patterned with low levels of cellular senescence/aging and mitochondrial stress, compared to those derived from 2D-culture environments. Notably, in contrast to current methods yielding mDA neurons without astrocyte differentiation, mDA neurons that differentiated from Og-NSCs were interspersed with astrocytes as in the physiologic brain environment. Thus, the Og-NSC-derived mDA neurons exhibited improved synaptic maturity, functionality, resistance to toxic insults, and faithful expressions of the midbrain-specific factors, in vitro and in vivo long after transplantation. Consequently, Og-NSC transplantation yielded potent therapeutic outcomes that are reproducible in PD model animals. Collectively, our observations demonstrate that the organoid-based method may satisfy the demands needed in the clinical setting of PD cell therapy.
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http://dx.doi.org/10.1016/j.pneurobio.2021.102086DOI Listing
May 2021

Downregulation of CR6-interacting factor 1 suppresses keloid fibroblast growth via the TGF-β/Smad signaling pathway.

Sci Rep 2021 01 12;11(1):500. Epub 2021 Jan 12.

Department of Medical Science, Chungnam National University, Daejeon, Republic of Korea.

Keloids are a type of aberrant skin scarring characterized by excessive accumulation of collagen and extracellular matrix (ECM), arising from uncontrolled wound healing responses. While typically non-pathogenic, keloids are occasionally regarded as a form of benign tumor. CR6-interacting factor 1 (CRIF1) is a well-known CR6/GADD45-interacting protein, that has both nuclear and mitochondrial functions, and also exerts regulatory effects on cell growth and apoptosis. In this study, cell proliferation, cell migration, collagen production and TGF-β signaling was compared between normal fibroblasts (NFs) and keloid fibroblasts (KFs). Subsequently, the effects of CRIF1 deficiency were investigated in both NFs and KFs. Cell proliferation, cell migration, collagen production and protein expressions of TGF-β, phosphorylation of Smad2 and Smad3 were all found to be higher in KFs compared to NFs. CRIF1 deficiency in NFs and KFs inhibited cell proliferation, migration, and collagen production. In addition, phosphorylation of Smad2 and Smad3, which are transcription factors of collagen, was decreased. In contrast, mRNA expression levels of Smad7 and SMURF2, two important inhibitory proteins of Smad2/3, were increased, suggesting that CRIF1 may regulate collagen production. CRIF1 deficiency decreases the proliferation and migration of KFs, thereby inhibiting their overgrowth via the transforming growth factor-β (TGF-β)/Smad pathway. CRIF1 may therefore represent a potential therapeutic target in keloid pathogenesis.
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http://dx.doi.org/10.1038/s41598-020-79785-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804403PMC
January 2021

SIRT1 Activation Attenuates the Cardiac Dysfunction Induced by Endothelial Cell-Specific Deletion of CRIF1.

Biomedicines 2021 Jan 8;9(1). Epub 2021 Jan 8.

Department of Physiology and Medical Science, College of Medicine, Chungnam National University, Daejeon 301-747, Korea.

The CR6-interacting factor1 (CRIF1) mitochondrial protein is indispensable for peptide synthesis and oxidative phosphorylation. Cardiomyocyte-specific deletion of CRIF1 showed impaired mitochondrial function and cardiomyopathy. We developed an endothelial cell-specific CRIF1 deletion mouse to ascertain whether dysfunctional endothelial CRIF1 influences cardiac function and is mediated by the antioxidant protein sirtuin 1 (SIRT1). We also examined the effect of the potent SIRT1 activator SRT1720 on cardiac dysfunction. Mice with endothelial cell-specific CRIF1 deletion showed an increased heart-to-body weight ratio, increased lethality, and markedly reduced fractional shortening of the left ventricle, resulting in severe cardiac dysfunction. Moreover, endothelial cell-specific CRIF1 deletion resulted in mitochondrial dysfunction, reduced ATP levels, inflammation, and excessive oxidative stress in heart tissues, associated with decreased SIRT1 expression. Intraperitoneal injection of SRT1720 ameliorated cardiac dysfunction by activating endothelial nitric oxide synthase, reducing oxidative stress, and inhibiting inflammation. Furthermore, the decreased endothelial junction-associated protein zonula occludens-1 in CRIF1-deleted mice was significantly recovered after SRT1720 treatment. Our results suggest that endothelial CRIF1 plays an important role in maintaining cardiac function, and that SIRT1 induction could be a therapeutic strategy for endothelial dysfunction-induced cardiac dysfunction.
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http://dx.doi.org/10.3390/biomedicines9010052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827654PMC
January 2021

Ref-1 protects against FeCl-induced thrombosis and tissue factor expression the GSK3β-NF-κB pathway.

Korean J Physiol Pharmacol 2021 Jan;25(1):59-68

Department of Physiology and Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea.

Arterial thrombosis and its associated diseases are considered to constitute a major healthcare problem. Arterial thrombosis, defined as blood clot formation in an artery that interrupts blood circulation, is associated with many cardiovascular diseases. Oxidative stress is one of many important factors that aggravates the pathophysiological process of arterial thrombosis. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ref-1) has a multifunctional role in cells that includes the regulation of oxidative stress and anti-inflammatory function. The aim of this study was to investigate the therapeutic effect of adenovirus-mediated Ref-1 overexpression on arterial thrombosis induced by 60% FeCl solution in rats. Blood flow was measured to detect the time to occlusion, thrombus formation was detected by hematoxylin and eosin staining, reactive oxygen species (ROS) levels were detected by high-performance liquid chromatography, and the expression of tissue factor and other proteins was detected by Western blot. FeCl aggravated thrombus formation in carotid arteries and reduced the time to artery occlusion. Ref-1 significantly delayed arterial obstruction the inhibition of thrombus formation, especially by downregulating tissue factor expression through the Akt-GSK3β-NF-κB signaling pathway. Ref1 also reduced the expression of vascular inflammation markers ICAM-1 and VCAM1, and reduced the level of ROS that contributed to thrombus formation. The results showed that adenovirus-mediated Ref-1 overexpression reduced thrombus formation in the rat carotid artery. In summary, Ref-1 overexpression had anti-thrombotic effects in a carotid artery thrombosis model and could be a target for the treatment of arterial thrombosis.
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http://dx.doi.org/10.4196/kjpp.2021.25.1.59DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756532PMC
January 2021

CR6 interacting factor 1 deficiency induces premature senescence via SIRT3 inhibition in endothelial cells.

Free Radic Biol Med 2020 04 25;150:161-171. Epub 2020 Feb 25.

Department of Physiology & Medical Science, Chungnam National University College of Medicine, Daejeon, 301-747, Republic of Korea. Electronic address:

Vascular endothelial cell senescence is an important cause of cardiac-related diseases. Mitochondrial reactive oxygen species (mtROS) have been implicated in cellular senescence and multiple cardiovascular disorders. CR6 interacting factor 1 (CRIF1) deficiency has been shown to increase mtROS via the inhibition of mitochondrial oxidative phosphorylation; however, the mechanisms by which mtROS regulates vascular endothelial senescence have not been thoroughly explored. The goal of this study was to investigate the effects of CRIF1 deficiency on endothelial senescence and to elucidate the underlying mechanisms. CRIF1 deficiency was shown to increase the activity of senescence-associated β-galactosidase along with increased expression of phosphorylated p53, p21, and p16 proteins. Cell cycle arrested in the G0/G1 phase were identified in CRIF1-deficient cells using the flow cytometry. Furthermore, CRIF1 deficiency was also shown to increase cellular senescence by reducing the expression of Sirtuin 3 (SIRT3) via ubiquitin-mediated degradation of transcription factors PGC1α and NRF2. Downregulation of CRIF1 also attenuated the function of mitochondrial antioxidant enzymes including manganese superoxide dismutase (MnSOD), Foxo3a, nicotinamide-adenine dinucleotide phosphate, and glutathione via the suppression of SIRT3. Interestingly, overexpression of SIRT3 in CRIF1-deficient endothelial cells not only reduced mtROS levels by elevating expression of the antioxidant enzyme MnSOD but also decreased the expression of cell senescence markers. Taken together, these results suggest that CRIF1 deficiency induces vascular endothelial cell senescence via ubiquitin-mediated degradation of the transcription coactivators PGC1α and NRF2, resulting in decreased expression of SIRT3.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.02.017DOI Listing
April 2020

CR6-interacting factor 1 deficiency reduces endothelial nitric oxide synthase activity by inhibiting biosynthesis of tetrahydrobiopterin.

Sci Rep 2020 01 21;10(1):842. Epub 2020 Jan 21.

Department of Physiology & Medical Science, School of Medicine, Chungnam National University, Daejeon, 301-747, Republic of Korea.

Downregulation of CR6 interacting factor 1 (CRIF1) has been reported to induce mitochondrial dysfunction, resulting in reduced activity of endothelial nitric oxide synthase (eNOS) and NO production in endothelial cells. Tetrahydrobiopterin (BH4) is an important cofactor in regulating the balance between NO (eNOS coupling) and superoxide production (eNOS uncoupling). However, whether the decreased eNOS and NO production in CRIF1-deficient cells is associated with relative BH4 deficiency-induced eNOS uncoupling remains completely unknown. Our results showed that CRIF1 deficiency increased eNOS uncoupling and depleted levels of total biopterin and BH4 by reducing the enzymes of BH4 biosynthesis (GCH-1, PTS, SPR, and DHFR) in vivo and vitro, respectively. Supplementation of CRIF1-deficient cells with BH4 significantly increased the recovery of Akt and eNOS phosphorylation and NO synthesis. In addition, scavenging ROS with MitoTEMPO treatment replenished BH4 levels by elevating levels of GCH-1, PTS, and SPR, but with no effect on the level of DHFR. Downregulation of DHFR synthesis regulators p16 or p21 in CRIF1-deficient cells partially recovered the DHFR expression. In summary, CRIF1 deficiency inhibited BH4 biosynthesis and exacerbated eNOS uncoupling. This resulted in reduced NO production and increased oxidative stress, which contributes to endothelial dysfunction and is involved in the pathogenesis of cardiovascular diseases.
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http://dx.doi.org/10.1038/s41598-020-57673-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972730PMC
January 2020

Dynamic Changes in the Bridging Collaterals of the Basal Ganglia Circuitry Control Stress-Related Behaviors in Mice.

Mol Cells 2020 Apr;43(4):360-372

Department of Life Sciences, Korea University, Seoul 02841, Korea.

The basal ganglia network has been implicated in the control of adaptive behavior, possibly by integrating motor learning and motivational processes. Both positive and negative reinforcement appear to shape our behavioral adaptation by modulating the function of the basal ganglia. Here, we examined a transgenic mouse line (G2CT) in which synaptic transmissions onto the medium spiny neurons (MSNs) of the basal ganglia are depressed. We found that the level of collaterals from direct pathway MSNs in the external segment of the globus pallidus (GPe) ('bridging collaterals') was decreased in these mice, and this was accompanied by behavioral inhibition under stress. Furthermore, additional manipulations that could further decrease or restore the level of the bridging collaterals resulted in an increase in behavioral inhibition or active behavior in the G2CT mice, respectively. Collectively, our data indicate that the striatum of the basal ganglia network integrates negative emotions and controls appropriate coping responses in which the bridging collateral connections in the GPe play a critical regulatory role.
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http://dx.doi.org/10.14348/molcells.2019.0279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191043PMC
April 2020

Carboxy-Terminal Region of a Thermostable CITase from Has the Ability to Produce Long Isomaltooligosaccharides.

J Microbiol Biotechnol 2019 Dec;29(12):1938-1946

Department of Agro-Food Resources, National Institute of Agricultural Sciences, Rural Development Administration, Jeonju 55365, Republic of Korea.

Isomaltooligosaccharides (IMOs) have good prebiotic effects, and long IMOs (LIMOs) with a degree of polymerization (DP) of 7 or above show improved effects. However, they are not yet commercially available, and require costly enzymes and processes for production. The Nterminal region of the thermostable cycloisomaltooligosaccharide glucanotransferase (TtCITase) shows cyclic isomaltooligosaccharide (CI)-producing activity owing to a catalytic domain of glycoside hydrolase (GH) family 66 and carbohydrate-binding module (CBM) 35. In the present study, we elucidated the activity of the C-terminal region of TtCITase (TtCITase-C; Met740-Phe1,559), including a CBM35-like region and the GH family 15 domain. The domain was successfully cloned, expressed, and purified as a single protein with a molecular mass of 115 kDa. TtCITase-C exhibited optimal activity at 40°C and pH 5.5, and retained 100% activity at pH 5.5 after 18-h incubation. TtCITase-C synthesized α-1,6 glucosyl products with over seven degrees of polymerization (DP) by an α-1,6 glucosyl transfer reaction from maltopentaose, isomaltopentaose, or commercialized maltodextrins as substrates. These results indicate that TtCITase-C could be used for the production of α-1,6 glucosyl oligosaccharides with over DP7 (LIMOs) in a more cost-effective manner, without requiring cyclodextran.
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http://dx.doi.org/10.4014/jmb.1910.10022DOI Listing
December 2019

CRIF1 deficiency induced mitophagy via p66shc-regulated ROS in endothelial cells.

Biochem Biophys Res Commun 2020 02 2;522(4):869-875. Epub 2019 Dec 2.

Department of Physiology & Medical Science, College of Medicine, Chungnam National University, Daejeon, 301-747, Republic of Korea. Electronic address:

Inhibition of mitochondrial protein CR6 interacting factor 1 (CRIF1) disturbs mitochondrial function, depolarizes membrane potential, and increases reactive oxygen species (ROS) levels in endothelial cells. Impaired mitochondrial function accompanied by oxidative damage is a major contributor to the initiation of mitophagy. We hypothesized that CRIF1 deficiency-induced harmful effects may promote mitophagy, and explored the mechanism underlying this effect in human umbilical vein endothelial cells (HUVECs). Our results showed that CRIF1 downregulation not only induced the mitophagy-related markers LC3 (LC3-II/Ⅰ), PTEN-induced putative kinase 1 (PINK1) and parkin, but also stimulated redox enzyme p66shc expression. Scavenging mitochondrial ROS markedly blunted the CRIF1 deficiency-induced increase in p66shc expression. In addition, knockdown of p66shc inhibited the CRIF1 deletion-triggered mitochondrial ROS increase, membrane potential depolarization, and mitochondrial fusion. The restoration of mitochondrial dysfunction by p66shc downregulation also decreased CRIF1 deficiency-induced mitophagy, by elevating the levels of LC3-II/Ⅰ, PINK1 and parkin. These findings suggest that CRIF1 deficiency induces mitophagy via p66shc-regulated ROS in endothelial cells.
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http://dx.doi.org/10.1016/j.bbrc.2019.11.109DOI Listing
February 2020

Far-Infrared-Emitting Sericite Board Upregulates Endothelial Nitric Oxide Synthase Activity through Increasing Biosynthesis of Tetrahydrobiopterin in Endothelial Cells.

Evid Based Complement Alternat Med 2019 31;2019:1813282. Epub 2019 Oct 31.

Department of Physiology & Medical Science, School of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.

Far-infrared ray (FIR) therapy has been reported to exert beneficial effects on cardiovascular function by elevating endothelial nitric oxide synthesis (eNOS) activity and nitric oxide (NO) production. Tetrahydrobiopterin (BH) is a key determinant of eNOS-dependent NO synthesis in vascular endothelial cells. However, whether BH synthesis is associated with the effects of FIR on eNOS/NO production has not yet been investigated. In this study, we investigated the effects of FIR on BH-dependent eNOS/NO production and vascular function. We used FIR-emitting sericite boards as an experimental material and placed human umbilical vein endothelial cells (HUVECs) and Sprague-Dawley rats on the boards with or without FIR irradiation and then evaluated vascular relaxation by detecting NO generation, BH synthesis, and Akt/eNOS activation. Our results showed that FIR radiation significantly enhanced Akt/eNOS phosphorylation and NO production in human endothelial cells and aorta tissues. FIR can also induce BH storage by elevating levels of enzymes (e.g., guanosine triphosphate cyclohydrolase-1, 6-pyruvoyl tetrahydrobiopterin synthase, sepiapterin reductase, and dihydrofolate reductase), which ultimately results in NO production. These results indicate that FIR upregulated eNOS-dependent NO generation via BH synthesis and Akt phosphorylation, which contributes to the regulation of vascular function. This might develop potential clinical application of FIR to treat vascular diseases by augmenting the BH/NO pathway.
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http://dx.doi.org/10.1155/2019/1813282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875339PMC
October 2019

Thermostable CITase from Thermoanaerobacter thermocopriae shows negative cooperativity.

Biotechnol Lett 2019 May 29;41(4-5):625-632. Epub 2019 Mar 29.

Department of Food Science and Technology, Chonnam National University, Gwangju, 61186, Republic of Korea.

Objective: The biochemical properties of a putative thermostable cycloisomaltooligosaccharide (CI) glucanotransferase gene from Thermoanaerobacter thermocopriae were determined using a recombinant protein (TtCITase) expressed in Escherichia coli and purified to a single protein.

Results: The 171-kDa protein displayed maximum activity at pH 6.0, and enzyme activity was stable at pH 5.0-11.0. The optimal temperature was 60 °C in 1 h incubation, and thermal stability of the protein was 63% at 60 °C for 24 h. TtCITase produced CI-7 to CI-17, as well as CI-18, CI-19, and CI-20, which are relatively large CIs. Additionally, an unusual kinetic feature of TtCITase was its negative cooperative behavior in the dextran T2000 cleavage reaction.

Conclusions: Based on our results, TtCITase can be applied to produce relatively large CIs at high temperature.
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http://dx.doi.org/10.1007/s10529-019-02666-6DOI Listing
May 2019

Isocitrate dehydrogenase 2 deficiency induces endothelial inflammation via p66sh-mediated mitochondrial oxidative stress.

Biochem Biophys Res Commun 2018 09 30;503(3):1805-1811. Epub 2018 Jul 30.

Department of Physiology & Medical Science, School of Medicine, Chungnam National University, Daejeon, 301-747, Republic of Korea. Electronic address:

Isocitrate dehydrogenase 2 (IDH2) is an essential enzyme in the mitochondrial antioxidant system, which produces nicotinamide adenine dinucleotide phosphate, and thereby defends against oxidative stress. We have shown that IDH2 downregulation results in mitochondrial dysfunction and reactive oxygen species (ROS) generation in mouse endothelial cells. The redox enzyme p66shc is a key factor in regulating the level of ROS in endothelial cells. In this study, we hypothesized that IDH2 knockdown-induced mitochondrial dysfunction stimulates endothelial inflammation, which might be regulated by p66shc-mediated oxidative stress. Our results showed that IDH2 downregulation led to mitochondrial dysfunction by decreasing the expression of mitochondrial oxidative phosphorylation complexes I, II, and IV, reducing oxygen consumption, and depolarizing mitochondrial membrane potential in human umbilical vein endothelial cells (HUVECs). The dysfunction not only increased mitochondrial ROS levels but also activated p66shc expression in HUVECs and IDH2 knockout mice. IDH2 deficiency increased intercellular adhesion molecule (ICAM)-1 expression and mRNA levels of pro-inflammatory cytokines (tumor necrosis factor [TNF]-α, and interleukin [IL]-1β) in HUVECs. The mRNA expression of ICAM-1 in endothelial cells and plasma levels of TNF-α and IL-1β were also markedly elevated in IDH2 knockout mice. However, p66shc knockdown rescued IDH2 deficiency-induced mitochondrial ROS levels, monocyte adhesion, ICAM-1, TNF-α, and IL-1β expression in HUVECs. These findings suggest that IDH2 deficiency induced endothelial inflammation via p66shc-mediated mitochondrial oxidative stress.
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http://dx.doi.org/10.1016/j.bbrc.2018.07.117DOI Listing
September 2018

Concentrations of Bisphenols in Canned Foods and Their Risk Assessment in Korea.

J Food Prot 2018 06;81(6):903-916

2 Department of Food and Nutrition, Duksung Women's University, Seoul, Korea.

The purpose of this study was to survey concentrations of bisphenols in canned foods using liquid chromatography-tandem mass spectrometry, to estimate the dietary exposure to bisphenols, and to assess the related risk for the Korean population from the intake of canned foods. The linearity of bisphenols in the range of 2.5 to 725 μg/L was satisfactory with correlation coefficients ( r) of 0.999. The limit of detection was 0.14 to 5.85 μg/L, and the limit of quantitation was 0.44 to 17.73 μg/L. Sample recoveries were 70.56 to 113.6%, with relative standard deviations below 10% for spiking levels of 50 and 250 μg/kg (15 and 75 μg/kg for BPS). The bisphenol concentrations in 104 canned foods ranged from undetectable to 1,525 μg/kg. The estimated mean daily intake of bisphenols was 0.54 to 78.69 ng/kg of body weight per day, and the 95th percentile daily intake was 1.92 to 134 ng/kg of body weight per day. Therefore, the intake of bisphenols from canned foods for the population in Korea is unlikely to cause human health problems. The analytical methods used are suitable for regular monitoring and assessment of human exposure to bisphenols from foods.
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http://dx.doi.org/10.4315/0362-028X.JFP-17-447DOI Listing
June 2018

PDE 5 inhibition with udenafil improves left ventricular systolic/diastolic functions and exercise capacity in patients with chronic heart failure with reduced ejection fraction; A 12-week, randomized, double-blind, placebo-controlled trial.

Am Heart J 2015 Jun 1;169(6):813-822.e3. Epub 2015 Apr 1.

Department of Internal Medicine, Seoul National University College of Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul.

Background: Impaired nitric oxide-mediated pulmonary vascular tone is commonly found in heart failure with reduced ejection fraction (HFrEF), and is associated with derangement of left ventricular (LV) hemodynamics and decreased exercise capacity, which may be reversed by PDE5 inhibitor. This study investigated the effects of a new, long-acting PDE5 inhibitor on LV hemodynamics and exercise capacity in HFrEF.

Methods: Patients with chronic HFrEF on optimal medical therapy for >30 days before enrollment were randomly assigned to placebo or udenafil at a dose of 50mg 2x/day for the first 4 weeks followed by 100mg 2x/day for the next 8 weeks. All patients underwent cardiopulmonary exercise echocardiography before and after the 12-week treatment.

Results: Improvement of subjective functional capacity was more frequently reported in the udenafil group (P = 0.002). Also, a higher increase in peak VO2 (Δpeak VO2, 21.6% (6.9 ~ 106.4%) vs 1.9% (-15.7 ~ 21.0%) in the placebo group, P = 0.04) and a larger decrease in ventilatory efficiency were observed in the udenafil group (Δ-6.4 ± 9.7 vs Δ1.9 ± 12.1 in the placebo group, P = 0.03). Regarding LV systolic function, the extent of increment in LV ejection fraction was significantly greater in the udenafil group (6.6 ± 6.4% vs 2.3 ± 4.8% in the placebo group, P = 0.02). In the udenafil group, an echocardiographic surrogate of LV filling pressure was more prominently decreased (P = 0.006) along with a significant reverse remodeling of left atrial volume index (57 ± 25mL at baseline to 44 ± 23 at 12th week, P = 0.04) and a progressive fall in B-type natriuretic peptide level (589 ± 679pg/mL at baseline to 220 ± 225pg/mL at 12th week, P < 0.001), indicating LV diastolic function improvement. Udenafil was well tolerated without excess of adverse events compared to placebo.

Conclusions: Udenafil improves LV systolic/diastolic functions and exercise capacity in conjunction with established conventional pharmacotherapy, without significant adverse events in HFrEF.
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http://dx.doi.org/10.1016/j.ahj.2015.03.018DOI Listing
June 2015

Variation of nephrotoxicity biomarkers by urinary storage condition in rats.

Toxicol Res 2014 Dec;30(4):305-9

Laboratory Animal Medicine, College of Veterinary Medicine, Chungbuk National University, Chungcheongbuk-do, Korea.

Recently, there has been an increase in the use of several nephrotoxicity biomarkers in preclinical experiments. In addition, it has been indicated that the result may have been influenced by secondary factors, such as sample storage condition or storage period. In this study, we have assessed the variation in urinary nephrotoxicity biomarkers as a result of urine storage conditions and storage period of the urine. Urine was sampled from specific pathogen-free Sprague-Dawley rats (19 weeks old), which were housed individually in hanged stainless steel wire mesh cages. Urine was stored at 20℃, at 4℃, or at -70℃ after sampling. The levels of the biomarkers such as beta-2 microglobulin (B2M), cystatin-C (Cys-C), N-acetyl-β- D-glucosaminidase (NAG), micro albumin (MA), micro protein (MP) were measured at 6, 24, 48 and 144 hr after sampling. The B2M level was significantly decreased at 6, 24, 48, and 144 hr compared to 0 hr at -70℃ (p < 0.05, p < 0.01, p < 0.05, and p < 0.05, respectively) and 24 and 144 hr at 20℃ (p < 0.01, p < 0.01, respectively). The Cys-C level was significantly decreased at 144 hr compared to 0 hr at 4℃ (p < 0.01), at 20℃ (p < 0.05) and at 70℃ (p < 0.01). MP and MA levels were not different for 144 hr in all storage conditions. Taken together, B2M and Cys-C levels were modulated by storage temperature and period. For the enhancement of test accuracy, it is suggested that strict protocols be established for samples to minimize the effects of the storage conditions on the detected levels of biomarkers.
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http://dx.doi.org/10.5487/TR.2014.30.4.305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289932PMC
December 2014

Consecutive cross-coupling reactions of 2,2-difluoro-1-iodoethenyl tosylate with boronic acids: efficient synthesis of 1,1-diaryl-2,2-difluoroethenes.

Beilstein J Org Chem 2013 14;9:2470-5. Epub 2013 Nov 14.

Department of Chemistry & Medical Chemistry, Yonsei University, 1 Yonseidae-gil, Wonju, Gangwondo 220-710, Republic of Korea.

The cross-coupling reactions of 2,2-difluoro-1-iodoethenyl tosylate (2) with 2 equiv of boronic acids in the presence of catalytic amounts of Pd(OAc)2 and Na2CO3 afforded the mono-coupled products 3 and 5 in high yields. The use of 4 equiv of boronic acids in the presence of catalytic amount of Pd(PPh3)2Cl2 and Na2CO3 in this reaction resulted in the formation of symmetrical di-coupled products 4 in high yields. Unsymmetrical di-coupled products 4 were obtained in high yields from the reactions of 3 with 2 equiv of boronic acids in the presence of catalytic amounts of Pd(OAc)2 and Na2CO3.
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http://dx.doi.org/10.3762/bjoc.9.286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869221PMC
December 2013

Total mercury, methylmercury and ethylmercury in marine fish and marine fishery products sold in Seoul, Korea.

Food Addit Contam Part B Surveill 2011 30;4(4):268-74. Epub 2011 Nov 30.

a Seoul Metropolitan Government Research Institute of Public Health and Environment , Seoul 427-070 , Republic of Korea.

In 2009, a survey of 177 samples of fish and fishery products from the markets in Seoul was carried out to investigate total mercury and organic mercury (methylmercury) concentrations and to establish a correlation, if any, between total and organic mercury levels. Concentrations of total and organic mercury in canned tuna ranged 0.001-2.581 and 0.003-1.307 mg/kg, respectively; those for fish, such as cod or salmon, ranged 0.012-2.529 and 0.021-0.507 mg/kg, respectively. Ethylmercury was not detected. More than 50% of total mercury in the samples existed as organic mercury. The correlation coefficients (r(2)) between total mercury and methylmercury concentrations of fish and fishery products found to have methylmercury were 0.844 and 0.976, respectively, which was statistically significant. There was a higher correlation in fishery products than in fish. Although there was no product in which mercury exceeded the standard set by the Food Code in 2008, with the exception of marlin steak, a processed food, which contained 1.307 mg/kg methylmercury. None exceeded the provisional tolerable weekly intake (PTWI) for mercury. Collectively, the results indicate that fish or fishery products marketed in Seoul, with the exception of marlin, have low levels of total or organic mercury and, thus, intake of these products is not a risk to public health.
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http://dx.doi.org/10.1080/19393210.2011.638087DOI Listing
December 2014

Isolation and characteristics of sorbitol-fermenting Escherichia coli O157 strains from cattle.

Microbes Infect 2006 Jul 23;8(8):2021-6. Epub 2006 May 23.

College of Veterinary Medicine, Chonbuk National University, Jeonju 561-756, Republic of Korea.

Cattle can be a reservoir of sorbitol-fermenting Escherichia coli O157 (SF E. coli O157) and a source of human diseases. In this study, six strains of SF E. coli O157 were isolated and characterized from cattle using an immunomagnetic separation procedure. PCR analysis of the SF E. coli O157 virulence markers showed that all six isolates tested positive for sfpA, rfbE and eaeA, and negative for terA, ureA, katP and espP. Two of the isolates contained the stx genes. Four isolates tested positive for enterohemorrhagic E. coli hlyA (EhlyA) by PCR but were nonhemolytic on the blood agar. Five isolates tested positive for the cdtA gene. The possession of these virulence factors was an indication of their pathogenic potential. The random amplified polymorphic DNA patterns, which were generated by the arbitrarily primed PCR of the SF E. coli O157 isolates from the cattle, were significantly different from those of the non-sorbitol-fermenting E. coli O157 (NSF E. coli O157) strains originating from cattle or humans. GelCompar analysis showed that the SF E. coli O157 isolates had only a 57% genetic similarity with the NSF E. coli strains. The minimal inhibitory concentration assay showed that imipenem inhibited the growth of the six isolates at a concentration of <4 microg/ml.
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http://dx.doi.org/10.1016/j.micinf.2006.03.002DOI Listing
July 2006