Publications by authors named "Seul Gi Kim"

56 Publications

Fisetin-induced PTEN expression reverses cellular senescence by inhibiting the mTORC2-Akt Ser473 phosphorylation pathway in vascular smooth muscle cells.

Exp Gerontol 2021 Dec 22;156:111598. Epub 2021 Oct 22.

Department of Pharmacology, College of Medicine, Yeungnam University, 170 Hyunchung-Ro, Nam-Gu, Daegu 42415, Republic of Korea; Smart-aging Convergence Research Center, College of Medicine, Yeungnam University, 170 Hyunchung-Ro, Nam-Gu, Daegu 42415, Republic of Korea. Electronic address:

Cellular senescence is caused by a wide range of intracellular and extracellular stimuli and influences physiological functions, leading to the progression of age-related diseases. Many studies have shown that cellular senescence is related to phosphatase and tension homolog deleted on chromosome ten (PTEN) loss and mammalian target of rapamycin (mTOR) activation. Although it has been reported that mTOR complex 1 (mTORC1) is major anti-aging target in several cell types, the functions and mechanisms of mTOR complex 2 (mTORC2) during aging have not been elucidated in vascular smooth muscle cells (VSMCs). Therefore, the aim of this study was to reveal the relationship between PTEN and mTORC2 during VSMC senescence. We found adriamycin-induced VSMC senescence was accompanied by reduced PTEN protein expression and upregulation of the mTORC2-Akt (Ser 473) pathway and that fisetin treatment reduced VSMC senescence by increasing PTEN and decreasing mTORC2 protein levels. Furthermore, PTEN played a primary role in the anti-aging effect of fisetin, and fisetin-activated PTEN directly regulated the mTORC2-Akt (Ser 473) signaling pathway, and attenuated senescence phenotypes such as senescence-associated β-galactosidase (SA-β-gal) and the p53-p21 signaling pathway in VSMCs. In mouse aortas, fisetin delayed aging by regulating the PTEN-mTORC2-Akt (Ser473) signaling pathway. These results suggest PTEN and mTORC2 are associated with cellular senescence in VSMCs and that the mTORC2-Akt (Ser 473) signaling pathway be considered a new target for preventing senescence-related diseases.
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http://dx.doi.org/10.1016/j.exger.2021.111598DOI Listing
December 2021

Real-Time Wireless Monitoring of Cell Proliferation and Detachment Based on pH-Responsive Conductive Polymer Dots.

Anal Chem 2021 06 10;93(24):8638-8646. Epub 2021 Jun 10.

Department of IT and Energy Convergence (BK21 FOUR), Korea National University of Transportation, Chungju 380-702, Republic of Korea.

wireless monitoring for cell proliferation and detachment kinetics was conducted using pH-responsive zwitterionic polymer dots (Z-PDs), based on changes in electrochemical signals derived from Z-PD-coated substrates the interaction of charges transferred between Z-PDs and cells. Z-PD-coated substrates were found to be a potent means to monitor and manipulate cell adhesion and detachment because of their high sensitivity over a wide range of pH conditions, and modification of the coated substrates was confirmed using a wireless system. At neutral pH, Z-PD-coated wireless sensors exhibited π-π stacking involving aromatic rings with hydrophobic interactions, thereby promoting cell proliferation; consequently, an increase in the measured resistance was observed. In contrast, Z-PD-coated substrates triggered by acidic and basic conditions promoted cell detachment, which induced an increase in the resistance compared with Z-PD substrates at pH 6.8, as a result of charges transferred to support Z-PD internalization through cell membranes after detachment. Therefore, as a wireless biosensor with excellent pH responsiveness that facilitates cell proliferation and detachment and whose electrochemical signals could be additionally acquired a smartphone, Z-PD biosensors demonstrated a more favorable approach for monitoring cell-surface interactions than conventional optically based methods.
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http://dx.doi.org/10.1021/acs.analchem.1c01778DOI Listing
June 2021

SIRT1 suppresses cellular senescence and inflammatory cytokine release in human dermal fibroblasts by promoting the deacetylation of NF-κB and activating autophagy.

Exp Gerontol 2021 07 6;150:111394. Epub 2021 May 6.

Department of Pharmacology, College of Medicine, Yeungnam University, Daegu, Republic of Korea; Smart-aging Convergence Research Center, College of Medicine, Yeungnam University, Daegu, Republic of Korea. Electronic address:

Skin aging is a complex process and involves extrinsic and intrinsic processes with distinct characteristics. Understanding skin aging requires knowledge of the senescence of human dermal fibroblasts (HDFs) and the biological mechanisms involved in this process. However, the molecular mechanism responsible for the aging of HDFs is still not clear. Therefore, we investigated mechanisms of autophagy, inflammation, and cellular senescence by Western blotting, immunofluorescence, real-time PCR, and senescence-associated β-galactosidase (SA-β-gal) staining in senescent HDFs. We found SRT1720 inhibited the inductions of inflammatory cytokines and cellular senescence by deacetylating acetyl-NF-κB levels and enhancing levels of autophagy-associated proteins and SIRT1 in senescent HDFs. However, the NF-κB activator prostratin attenuated signals associated with autophagy, such as those of LC3-II and Beclin-1, but increased inflammatory cytokine levels and cellular senescence. Notably, the expression levels of SIRT1 and autophagy-associated proteins were higher in aged mice administered SRT1720 than in old mice, and SRT1720 also decreased levels of acetyl-NF-κB, inflammatory cytokines, and senescence markers, which was in accord with in vitro results. These findings support that SRT1720 acts as an anti-aging agent and inhibits the inductions of inflammatory cytokines and senescence by regulating the SIRT1/acetyl-NF-κB signaling pathway and activating autophagy in senescent HDFs.
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http://dx.doi.org/10.1016/j.exger.2021.111394DOI Listing
July 2021

How antisolvent miscibility affects perovskite film wrinkling and photovoltaic properties.

Nat Commun 2021 Mar 10;12(1):1554. Epub 2021 Mar 10.

School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon, Korea.

Charge carriers' density, their lifetime, mobility, and the existence of trap states are strongly affected by the microscopic morphologies of perovskite films, and have a direct influence on the photovoltaic performance. Here, we report on micro-wrinkled perovskite layers to enhance photocarrier transport performances. By utilizing temperature-dependent miscibility of dimethyl sulfoxide with diethyl ether, the geometry of the microscopic wrinkles of the perovskite films are controlled. Wrinkling is pronounced as temperature of diethyl ether (T) decreases due to the compressive stress relaxation of the thin rigid film-capped viscoelastic layer. Time-correlated single-photon counting reveals longer carrier lifetime at the hill sites than at the valley sites. The wrinkled morphology formed at T = 5 °C shows higher power conversion efficiency (PCE) and better stability than the flat one formed at T = 30 °C. Interfacial and additive engineering improve further PCE to 23.02%. This study provides important insight into correlation between lattice strain and carrier properties in perovskite photovoltaics.
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http://dx.doi.org/10.1038/s41467-021-21803-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946869PMC
March 2021

Capturing Mobile Lithium Ions in a Molecular Hole Transporter Enhances the Thermal Stability of Perovskite Solar Cells.

Adv Mater 2021 Mar 19;33(12):e2007431. Epub 2021 Feb 19.

School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon, 440-746, Korea.

A thermally stable perovskite solar cell (PSC) based on a new molecular hole transporter (MHT) of 1,3-bis(5-(4-(bis(4-methoxyphenyl) amino)phenyl)thieno[3,2-b]thiophen-2-yl)-5-octyl-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione (coded HL38) is reported. Hole mobility of 1.36 × 10 cm V s and glass transition temperature of 92.2 °C are determined for the HL38 doped with lithium bis(trifluoromethanesulfonyl)imide and 4-tert-butylpyridine as additives. Interface engineering with 2-(2-aminoethyl)thiophene hydroiodide (2-TEAI) between the perovskite and the HL38 improves the power conversion efficiency (PCE) from 19.60% (untreated) to 21.98%, and this champion PCE is even higher than that of the additive-containing 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (spiro-MeOTAD)-based device (21.15%). Thermal stability testing at 85 °C for over 1000 h shows that the HL38-based PSC retains 85.9% of the initial PCE, while the spiro-MeOTAD-based PSC degrades unrecoverably from 21.1% to 5.8%. Time-of-flight secondary-ion mass spectrometry studies combined with Fourier transform infrared spectroscopy reveal that HL38 shows lower lithium ion diffusivity than spiro-MeOTAD due to a strong complexation of the Li with HL38, which is responsible for the higher degree of thermal stability. This work delivers an important message that capturing mobile Li in a hole-transporting layer is critical in designing novel MHTs for improving the thermal stability of PSCs. In addition, it also highlights the impact of interface design on non-conventional MHTs.
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http://dx.doi.org/10.1002/adma.202007431DOI Listing
March 2021

Comparative efficacy and tolerability of third-line treatments for advanced gastric cancer: A systematic review with Bayesian network meta-analysis.

Eur J Cancer 2021 02 15;144:49-60. Epub 2020 Dec 15.

Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, South Korea; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea. Electronic address:

Background: The most effective agent for the third-line treatment of advanced/metastatic gastric cancer (AGC) has not yet been determined. The aim of this network meta-analysis is to compare the relative efficacy and tolerability of third-line treatments for AGC.

Materials And Methods: We conducted a comprehensive literature review of randomised clinical trials (RCTs) using four electronic databases. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events (AEs) were used as efficacy or tolerability outcomes. A Bayesian network meta-analysis with a random-effects model was used.

Results: Seven RCTs involving 2601 patients and nine treatments were included. The results suggested that 1 mg/kg nivolumab (nivolumab1) + 3 mg/kg ipilimumab (ipilimumab3) (hazard ratio [HR] 0.59, 95% credible interval [Crl] 0.38-0.91) was the most effective treatment, followed by nivolumab (HR 0.63, 95% Crl 0.50-0.79), for prolonging OS. Regorafenib (HR 0.40, 95% Crl 0.28-0.58) was most likely to improve PFS, followed by apatinib (HR 0.45, 95% Crl 0.33-0.60). Nivolumab1 + ipilimumab3 and nivolumab were better at improving ORR, whereas nivolumab1 + ipilimumab3 had the highest toxicity based on the AEs. For benefit-risk ratio, nivolumab, apatinib or regorafenib appeared to be the best options. Chemotherapy or two different dose combinations of nivolumab and ipilimumab were ranked as the next options because of poor tolerability, despite good efficacy.

Conclusion: Immunotherapy (nivolumab) or antiangiogenic agents (regorafenib and apatinib) are associated with benefits for benefit-risk ratio as third-line monotherapy. This study might serve as a guideline to aid in the selection of third-line treatments for AGC.
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http://dx.doi.org/10.1016/j.ejca.2020.10.030DOI Listing
February 2021

Fall characteristics among elderly populations in urban and rural areas in Korea.

Medicine (Baltimore) 2020 Nov;99(46):e23106

Department of Rehabilitation Medicine, Hanyang University, College of Medicine.

Falling is one of the leading causes of injury among elderly populations. As the population over 65 years old increases, medical costs due to falling will also increase. Urban and rural areas have different fall characteristics, and research into these differences is lacking.A survey was conducted on 2012 people over 60 years old between September 1, 2015, to October 12, 2015. Guro-gu (Seoul), Yeongdeungpo-gu (Seoul), and Jung-gu (Daegu) were classified as urban areas and included 1205 of the study participants. Dalseong-gun (Daegu) and Yangpyeong-gun (Gyeonggi-do) were categorized as rural areas and included 807 participants. The survey included questions about fall history, cause, season and time of recent falls, and external conditions associated with recent falls, like floor or ground materials and shoe types.Rural respondents were older than urban respondents (P < .001) but did not differ significantly in gender proportion (P = .082). Fall history over the past year was not different between the 2 regions (P = .693), but lifetime fall history was greater among rural respondents (P < .001). Only 5.1% of all respondents had undergone fall-prevention education. A slippery floor was the most common cause of falls in both regions, but there was a significant difference in pattern of fall causes (P < .001). Falls were more frequent in the summer, spring, and the afternoon in urban areas, and in the summer, autumn, and the morning in rural areas. Cement and asphalt were the most common ground materials at the time of falls in both regions, but rural respondents had higher fall rates when walking on soil and when wearing slippers.A fall-prevention program that reflects the characteristics and differences of falls in urban and rural areas should be developed and used to effectively prevent falling among elderly people.
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http://dx.doi.org/10.1097/MD.0000000000023106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668504PMC
November 2020

Dual-labeled prostate-specific membrane antigen (PSMA)-targeting agent for preoperative molecular imaging and fluorescence-guided surgery for prostate cancer.

J Labelled Comp Radiopharm 2021 01 15;64(1):4-13. Epub 2020 Oct 15.

Department of Nuclear Medicine and Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, Iksan, South Korea.

The objective of this study was to report the synthesis and characteristics of a dual modality imaging agent, Tc-99m GRFLTGGTGRLLRIS-GHEG-ECG-K(-5-carboxy-X-rhodamine)-NH (GRFLT-ECG-ROX), and to verify its feasibility as both molecular imaging and intraoperative guidance agent. GRFLT-ECG-ROX was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of GRFLT-ECG-ROX with Tc-99m was accomplished using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed using LNCaP and PC-3 tumor-bearing murine models. Surgical removal of tumor nodules in murine models with peritoneal carcinomatosis was performed under a fluorescence imaging system. After radiolabeling procedures with Tc-99m, Tc-99m GRFLT-ECG-ROX complexes were prepared in high yield (>96%). The binding affinity value (K ) of Tc-99m GRFLT-ECG-ROX for LNCaP cells was estimated to be 9.5 ± 1.3 nM. In gamma camera imaging, the tumor to normal muscle uptake ratios of Tc-99m GRFLT-ECG-ROX increased with time (3.1 ± 0.2, 4.0 ± 0.4, and 6.3 ± 0.9 at 1, 2, and 3 h, respectively). Under real-time optical imaging, the removal of visible nodules was successfully performed. Thus, Tc-99m GRFLT-ECG-ROX could provide both preoperative molecular imaging and fluorescence imaging guidance for tumor removal.
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http://dx.doi.org/10.1002/jlcr.3884DOI Listing
January 2021

Prednisolone suppresses adriamycin-induced vascular smooth muscle cell senescence and inflammatory response via the SIRT1-AMPK signaling pathway.

PLoS One 2020 30;15(9):e0239976. Epub 2020 Sep 30.

Department of Pharmacology, College of Medicine, Yeungnam University, Daegu, Republic of Korea.

Cellular senescence is associated with inflammation and the senescence-associated secretory phenotype (SASP) of secreted proteins. Vascular smooth muscle cell (VSMC) expressing the SASP contributes to chronic vascular inflammation, loss of vascular function, and the developments of age-related diseases. Although VSMC senescence is well recognized, the mechanism of VSMC senescence and inflammation has not been established. In this study, we aimed to determine whether prednisolone (PD) attenuates adriamycin (ADR)-induced VSMC senescence and inflammation through the SIRT1-AMPK signaling pathway. We found that PD inhibited ADR-induced VSMC senescence and inflammation response by decreasing p-NF-κB expression through the SIRT1-AMPK signaling pathway. In addition, Western blotting revealed PD not only increased SIRT1 expression but also increased the phosphorylation of AMPK at Ser485 in ADR-treated VSMC. Furthermore, siRNA-mediated downregulation or pharmacological inhibitions of SIRT1 or AMPK significantly augmented ADR-induced inflammatory response and senescence in VSMC despite PD treatment. In contrast, the overexpression of SIRT1 or constitutively active AMPKα (CA-AMPKα) attenuated cellular senescence and p-NF-κB expression. Taken together, the inhibition of p-NF-κB by PD through the SIRT1 and p-AMPK (Ser485) pathway suppressed VSMC senescence and inflammation. Collectively, our results suggest that anti-aging effects of PD are caused by reduced VSMC senescence and inflammation due to reciprocal regulation of the SIRT1/p-AMPK (Ser485) signaling pathway.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239976PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526920PMC
December 2020

NIR-vis-Induced pH-Sensitive TiO Immobilized Carbon Dot for Controllable Membrane-Nuclei Targeting and Photothermal Therapy of Cancer Cells.

ACS Appl Mater Interfaces 2020 Aug 12;12(34):37929-37942. Epub 2020 Aug 12.

Department of Green Bio Engineering, Korea National University of Transportation, Chungju 380-702, Republic of Korea.

This study investigated a selective and sensitive theragnosis system for the specific targeting of the membrane and nuclei based on visible-light and pH-responsive TiO-integrated cross-linked carbon dot (C-CD/TiO) for tumor detection and controllable photothermal therapy. The cross-linking system was formed by boronate ester linkages between the TiO-immobilized Dopa-decyl (D-CD) and zwitterionic-formed CD (Z-CD) for nuclear targeting, which showed fluorescence "off" at physiological pH. The fluorescence recovered to the "on" state in acidic cancer cells owing to cleavages of the boronate ester bonds, resulting in the disruption of the Förster resonance energy transfer that generated different CDs useful for tumor-selective biosensors and therapy. D-CD, which is hydrophobic, can penetrate the hydrophobic sites of the cell membrane; it caused a loss in the hydrophobicity of these sites after visible-light irradiation. This was achieved by the photocatalytic activity of the TiO modulating energy bandgap, whereas the Z-CD targeted the nucleus, as confirmed by merged confocal microscopy images. D-CD augmented by photothermal heat also exhibited selective anticancer activity in the acidic tumor condition but showed only minimal effects at a normal site at pH 7.4. After C-CD/TiO injection to an tumor model, C-CD/TiO efficiently ablated tumors under NIR light irradiation. The C-CD/TiO group showed up-regulation of the pro-apoptotic markers such as and in tumor. This material exhibited its potential as a theragnostic sensor with excellent biocompatibility, high sensitivity, selective imaging, and direct anticancer activity via photothermal therapy.
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http://dx.doi.org/10.1021/acsami.0c11979DOI Listing
August 2020

Selective elimination of human pluripotent stem cells by Anti-Dsg2 antibody-doxorubicin conjugates.

Biomaterials 2020 11 13;259:120265. Epub 2020 Aug 13.

Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea; Department of Biomolecular Science, KRIBB School of Bioscience, Korea University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon, 34113, Republic of Korea. Electronic address:

The self-renewal properties of human pluripotent stem cells (hPSCs) contribute to their efficacy in tissue regeneration applications yet increase the likelihood of teratoma formation, thereby limiting their clinical utility. To address this issue, we developed a tool to specifically target and neutralize undifferentiated hPSCs, thereby minimizing tumorigenicity risk without negatively affecting regenerated and somatic tissues. Specifically, we conjugated a monoclonal antibody (K6-1) previously generated in our laboratory against desmoglein 2 (Dsg2), which is highly differentially expressed in undifferentiated hPSCs versus somatic tissues, to the chemotherapeutic agent doxorubicin (DOX). The K6-1-DOX conjugates were selectively targeted and incorporated into Dsg2-positive hPSCs, leading to pH-dependent endosomal release and nuclear localization of DOX with subsequent cytotoxicity via an apoptotic caspase cascade. Conversely, Dsg2-negative fibroblasts showed minimal conjugate uptake or cytotoxicity, suggesting that K6-1-DOX treatment would yield few side effects owing to off-target effects. Selective removal of undifferentiated stem cells was also supported by in vivo studies using a mouse xenograft model, wherein hIgG-DOX- but not K6-1-DOX-pretreated-hPSC injection led to teratoma development. Together, these results validated the ability of the Dsg2-targeted antibody-anticancer drug conjugate to facilitate the safety of stem cell therapies.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120265DOI Listing
November 2020

Nifedipine-induced AMPK activation alleviates senescence by increasing autophagy and suppressing of Ca levels in vascular smooth muscle cells.

Mech Ageing Dev 2020 09 15;190:111314. Epub 2020 Jul 15.

Department of Pharmacology, College of Medicine, Yeungnam University, 170 Hyunchung-Ro, Nam-Gu, Daegu 42415, Republic of Korea; Smart-aging Convergence Research Center, College of Medicine, Yeungnam University, 170 Hyunchung-Ro, Nam-Gu, Daegu 42415, Republic of Korea. Electronic address:

Calcium (Ca) homeostasis is disrupted during aging in several cell types and this disruption leads to autophagy impairment. The mechanisms regarding Ca, senescence, and autophagy need to be elucidated. Therefore, we hypothesized that cellular senescence can be improved by regulating Ca level and autophagy activity. We identified that hydrogen peroxide (HO)-induced senescence was accompanied by Ca elevation, impairment of autophagic flux and increase of mammalian target of rapamycin (mTOR) phosphorylation in VSMCs. The treatment of nifedipine dose-dependently suppressed HO-induced senescence by reducing Ca entry, autophagy impairment and mTOR signaling, and this suppression was found to be related to senescence-associated β-galactosidase (SA-β-gal) activity and the expressions of senescence marker protein 30 (SMP30), p53, and p21. Furthermore, HO-induced autophagy impairment also accelerated senescence and accumulations of ubiquitinated proteins. AMPK inhibition or transfection with AMPK siRNA showed that the anti-senescence effect of nifedipine involved AMPK activation. These results suggest nifedipine-inducted AMPK activation suppresses VSMC senescence by regulating autophagic flux and Ca levels.
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http://dx.doi.org/10.1016/j.mad.2020.111314DOI Listing
September 2020

Diselenide-Bridged Carbon-Dot-Mediated Self-Healing, Conductive, and Adhesive Wireless Hydrogel Sensors for Label-Free Breast Cancer Detection.

ACS Nano 2020 07 12;14(7):8409-8420. Epub 2020 Jun 12.

Department of Chemical & Biological Engineering, Korea National University of Transportation, Chungju 380-702, Republic of Korea.

Recently, a great deal of research has focused on the study of self-healing hydrogels possessing electronic conductivity due to their wide applicability for use in biosensors, bioelectronics, and energy storage. The low solubility, poor biocompatibility, and lack of effective stimuli-responsive properties of their sp carbon-rich hybrid organic polymers, however, have proven challenging for their use in electroconductive self-healing hydrogel fabrication. In this study, we developed stimuli-responsive electrochemical wireless hydrogel biosensors using ureidopyriminone-conjugated gelatin (Gel-UPy) hydrogels that incorporate diselenide-containing carbon dots (dsCD) for cancer detection. The cleavage of diselenide groups of the dsCD within the hydrogels by glutathione (GSH) or reactive oxygen species (ROS) initiates the formation of hydrogen bonds that affect the self-healing ability, conductivity, and adhesiveness of the Gel-UPy/dsCD hydrogels. The Gel-UPy/dsCD hydrogels demonstrate more rapid healing under tumor conditions (MDA-MB-231) compared to that observed under physiological conditions (MDCK). Additionally, the cleavage of diselenide bonds affects the electrochemical signals due to the degradation of dsCD. The hydrogels also exhibit excellent adhesiveness and cancer detection ability after exposure to a high concentration of GSH or ROS, and this is comparable to results observed in a low concentration environment. Based on the combined self-healing, conductivity, and adhesiveness properties of the Gel-UPy/dsCD, this hydrogel exhibits promise for use in biomedical applications, particularly those that involve cancer detection, due to its selectivity and sensitivity under tumor conditions.
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http://dx.doi.org/10.1021/acsnano.0c02517DOI Listing
July 2020

SRT1720-induced activation of SIRT1 alleviates vascular smooth muscle cell senescence through PKA-dependent phosphorylation of AMPKα at Ser485.

FEBS Open Bio 2020 07 5;10(7):1316-1325. Epub 2020 Jun 5.

Department of Pharmacology, College of Medicine, Yeungnam University, Daegu, Korea.

Aging is a major risk factor for hypertension and atherosclerosis, and vascular smooth muscle cell (VSMC) senescence can promote aging-related vascular diseases. Sirtuin-1 (SIRT1) and AMP-activated protein kinase (AMPK) were previously reported to modulate vascular senescence; however, its effects have not been well characterized. To determine the nature of the interaction between SIRT1 and AMPK in VSMC senescence, we investigated the effects of SRT1720 on its downstream targets of SIRT1 and the phosphorylation of AMPKα at Ser485. During Adriamycin-induced VSMC senescence, SRT1720 increased the activity of SIRT1 and AMPKα phosphorylation at Ser485 via the cAMP-protein kinase A (PKA) pathway. Telomere length and telomerase reverse transcriptase expression were increased by SIRT1 activation with SRT1720. Taken together, these data show that activation of the SIRT1/cAMP-PKA/p-AMPKα (Ser485) pathway may be an effective antisenescence mechanism for VSMCs.
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http://dx.doi.org/10.1002/2211-5463.12895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327920PMC
July 2020

Quercetin-induced apoptosis ameliorates vascular smooth muscle cell senescence through AMP-activated protein kinase signaling pathway.

Korean J Physiol Pharmacol 2020 Jan 20;24(1):69-79. Epub 2020 Dec 20.

Department of Pharmacology, Yeungnam University College of Medicine, Daegu 42415, Korea.

Aging is one of the risk factors for the development of cardiovascular diseases. During the progression of cellular senescence, cells enter a state of irreversible growth arrest and display resistance to apoptosis. As a flavonoid, quercetin induces apoptosis in various cells. Accordingly, we investigated the relationship between quercetin-induced apoptosis and the inhibition of cellular senescence, and determined the mechanism of oxidative stress-induced vascular smooth muscle cell (VSMC) senescence. In cultured VSMCs, hydrogen peroxide (HO) dose-dependently induced senescence, which was associated with increased numbers of senescence-associated β-galactosidase-positive cells, decreased expression of SMP30, and activation of p53-p21 and p16 pathways. Along with senescence, expression of the anti-apoptotic protein Bcl-2 was observed to increase and the levels of proteins related to the apoptosis pathway were observed to decrease. Quercetin induced apoptosis through the activation of AMP-activated protein kinase. This action led to the alleviation of oxidative stress-induced VSMC senescence. Furthermore, the inhibition of AMPK activation with compound C and siRNA inhibited apoptosis and aggravated VSMC senescence by reversing p53-p21 and p16 pathways. These results suggest that senescent VSMCs are resistant to apoptosis and quercetin-induced apoptosis attenuated the oxidative stress-induced senescence through activation of AMPK. Therefore, induction of apoptosis by polyphenols such as quercetin may be worthy of attention for its anti-aging effects.
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http://dx.doi.org/10.4196/kjpp.2020.24.1.69DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940493PMC
January 2020

Anterior Approach Following Intraoperative Reduction for Cervical Facet Fracture and Dislocation.

J Korean Neurosurg Soc 2020 Mar 9;63(2):202-209. Epub 2019 Dec 9.

Department of Neurosurgery, College of Medicine, Chosun University, Gwangju, Korea.

Objective: The purpose of this study was to evaluate the efficacy of the anterior approach following intraoperative reduction under general anesthesia in patients with cervical facet fracture and dislocation.

Methods: Twenty-three patients with single level cervical facet fracture and dislocation who were subjected to the anterior approach alone following immediate intraoperative reduction under general anesthesia from March 2013 to December 2017 were enrolled in this study. Neurological status, clinical outcome, and radiological studies were evaluated preoperatively, postoperatively, and during the follow-up period.

Results: The cohort comprised 15 men and eight women with a mean age of 57 years (from 24 to 81). All patients were operated on within the first 8 hours following the injury. After gentle manual reduction or closed reduction with Gardner-Wells traction, under general anesthesia monitored by somatosensory-evoked potentials, all operations were successfully completed using the anterior approach alone except in two patients, who had a risk of over-distraction. In them, a satisfactory gentle manual reduction or closed reduction was not possible, and required open posterior reduction of the locked facets followed by anterior cervical discectomy and fusion. In one patient, screw retropulsion was observed in 1 month after surgery. There were no reduction-related complications or neurological aggravations after surgery. All patients showed evidence of stability at the instrumented level at the final follow-up (mean follow-up, 12 months).

Conclusion: Anterior approach following intraoperative reduction monitored by somatosensory-evoked potentials under general anesthesia for cervical dislocation and locked facets is a relatively safe and effective alternative when cervical alignment is achieved by intraoperative reduction.
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http://dx.doi.org/10.3340/jkns.2019.0139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054114PMC
March 2020

Bioelectrical Impedance Analysis Is Not Sufficient for Determining Water Deficit in Hypernatremic Patients.

Med Sci Monit 2019 Nov 9;25:8438-8446. Epub 2019 Nov 9.

Department of Internal Medicine, College of Medicine, Konyang University, Daejeon, South Korea.

BACKGROUND Hypernatremia is associated with poor outcomes in critically ill patients, and an accurate assessment of water volume is important to determine appropriate fluid hydration. Bioelectrical impedance analysis (BIA) is a new, noninvasive, and relatively easy method for measuring hydration status. This study aimed to investigate whether bioelectrical impedance measurements of body water could reduce the frequency of blood sampling for fluid replacement in patients with hypernatremia. MATERIAL AND METHODS Fifty-one hospitalized patients were studied with hypernatremia, defined as a serum sodium ≥150 mmol/L determined by laboratory testing. Laboratory and BIA measurements were compared, and water deficiency was calculated with a conventional formula (sodium-corrected Watson formula) and measured by BIA. RESULTS The value of the absolute fluid overload (AFO) equivalent to the overhydration (OH) value, determined using BIA, did not accurately represent water deficit in patients with hypernatremia (r=0.137, P=0.347). Although the total body water (TBW) measured by BIA showed a significant correlation with that determined by the conventional formula (r=0.861, P<0.001), there was a proportional bias (r=0.617, P<0.001). The intracellular water (ICW) measured by BIA underestimated the TBW level calculated by the conventional formula by about 14.06±4.0 L in the Bland-Altman analysis. CONCLUSIONS It is not currently possible to replace blood testing with BIA for assessing volume status in hypernatremic patients. However, ICW value measured by BIA might represent plasma sodium level more accurately than extracellular water (ECW) or TBW value in patients with hypernatremia.
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http://dx.doi.org/10.12659/MSM.918095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863038PMC
November 2019

Reduction-Triggered Paclitaxel Release Nano-Hybrid System Based on Core-Crosslinked Polymer Dots with a pH-Responsive Shell-Cleavable Colorimetric Biosensor.

Int J Mol Sci 2019 Oct 28;20(21). Epub 2019 Oct 28.

Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungju 380-702, Korea.

Herein, we describe the fabrication and characterization of carbonized disulfide core-crosslinked polymer dots with pH-cleavable colorimetric nanosensors, based on diol dye-conjugated fluorescent polymer dots (L-PD), for reduction-triggered paclitaxel (PTX) release during fluorescence imaging-guided chemotherapy of tumors. L-PD were loaded with PTX (PTX loaded L-PD), via π-π stackings or hydrophobic interactions, for selective theragnosis by enhanced release of PTX after the cleavage of disulfide bonds by high concentration of glutathione (GSH) in a tumor. The nano-hybrid system showed fluorescence quenching behavior with less than 2% of PTX released under physiological conditions. However, in a tumor microenvironment, the fluorescence recovered at an acidic-pH, and PTX (approximately 100% of the drug release) was released efficiently out of the matrix by reduction caused by the GSH level in the tumor cells, which improved the effectiveness of the cancer treatment. Therefore, the colorimetric nanosensor showed promising potential in distinguishing between normal and cancerous tissues depending on the surrounding pH and GSH concentrations so that PTX can be selectively delivered into cancer cells for improved cancer diagnosis and chemotherapy.
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http://dx.doi.org/10.3390/ijms20215368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862247PMC
October 2019

Multifunctional Chemical Linker Imidazoleacetic Acid Hydrochloride for 21% Efficient and Stable Planar Perovskite Solar Cells.

Adv Mater 2019 Sep 12;31(39):e1902902. Epub 2019 Aug 12.

School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Korea.

Chemical interaction at a heterojunction interface induced by an appropriate chemical linker is of crucial importance for high efficiency, hysteresis-less, and stable perovskite solar cells (PSCs). Effective interface engineering in PSCs is reported via a multifunctional chemical linker of 4-imidazoleacetic acid hydrochloride (ImAcHCl) that can provide a chemical bridge between SnO and perovskite through an ester bond with SnO via esterification reaction and an electrostatic interaction with perovskite via imidazolium cation in ImAcHCl and iodide anion in perovskite. In addition, the chloride anion in ImAcHCl plays a role in the improvement of crystallinity of perovskite film crystallinity. The introduction of ImAcHCl onto SnO realigns the positions of the conduction and valence bands upwards, reduces nonradiative recombination, and improves carrier life time. As a consequence, average power conversion efficiency (PCE) is increased from 18.60% ± 0.50% to 20.22% ± 0.34% before and after surface modification, respectively, which mainly results from an enhanced voltage from 1.084 ± 0.012 V to 1.143 ± 0.009 V. The best PCE of 21% is achieved by 0.1 mg mL ImAcHCl treatment, along with negligible hysteresis. Moreover, an unencapsulated device with ImAcHCl-modified SnO shows much better thermal and moisture stability than unmodified SnO .
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http://dx.doi.org/10.1002/adma.201902902DOI Listing
September 2019

The effect of compositional engineering of imidazolium lead iodide on the resistive switching properties.

Nanoscale 2019 Aug;11(30):14455-14464

School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea.

We report here resistive switching memory characteristics of imidazolium lead iodide depending on the molar ratio of PbI2 to imidazolium iodide (ImI), that is, PbI2 : ImI = 1 : 0, 1 : 0.5, 1 : 1, 1 : 2, 1 : 3 and 0 : 1. X-ray diffraction confirms that the stoichiometric composition results in a hexagonal structure of (Im)PbI3, showing a one-dimensional face-sharing [PbI3-] chain. Bipolar resistive switching characteristics are observed regardless of the mixing ratio, where the forming process is required prior to SET and RESET processes at around +0.2 V and -0.2 V, respectively. The ON/OFF ratio is increased from 106 to 109 as the ImI content is increased due to the increased HRS associated with the pronounced insulating characteristics by ImI, whereas, the stoichiometric (Im)PbI3 exhibits 5 times longer endurance (103) and an order of magnitude longer retention time (104 s) as compared to other compositions. Multilevel data storage capability is confirmed by changing the compliance current. The low resistance state (LRS) and the high resistance state (HRS) are associated with Ohmic conduction and Schottky conduction, respectively. Density functional theory (DFT) calculation reveals that the defect formation energy of iodine vacancy is estimated to be low indicating that (Im)PbI3 has a sufficient concentration of iodide vacancy for filament formation. Further energy barrier calculations show that iodide migration preferentially occurs along the 1-dimensional [234] crystallographic direction rather than the interlayer [130] direction. A good performance of the (Im)PbI3-based memristor is thus related to the low defect formation energy of iodide vacancy and the preferential growth of the filament along the 1-dimensional chain.
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http://dx.doi.org/10.1039/c9nr02885dDOI Listing
August 2019

A novel dual-modality imaging agent targeting folate receptor of tumor for molecular imaging and fluorescence-guided surgery.

Ann Nucl Med 2019 Aug 27;33(8):606-616. Epub 2019 May 27.

Department of Nuclear Medicine and Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, 344-2 Shinyong-Dong, Iksan, Jeollabuk-do, 570-711, Republic of Korea.

Objective: Folate receptor (FR) is an ideal target for cancer imaging because it is frequently overexpressed in major types of human tumor, whereas its expression in normal organs is highly limited. Combining nuclear and fluorescence-imaging techniques provides a novel approach for cancer imaging and monitoring the surgery. The objective of this study was to report the synthesis and characteristics of a dual-modality imaging agent, Tc-99m Folate-Gly-His-Glu-Gly-Glu-Cys-Gly-Lys(-5-carboxy-X-rhodamine)-NH (Folate-ECG-ROX), and verify its feasibility as both molecular imaging agent and intra-operative guidance.

Methods: Folate-ECG-ROX was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of Folate-ECG-ROX with Tc-99m was done using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution and ex vivo imaging studies were performed using KB and HT-1080 tumor-bearing murine models. Tumor tissue slides were prepared and analyzed with immunohistochemistry staining and confocal microscopy. Surgical removal of tumor nodules in murine models with peritoneal carcinomatosis was performed under the fluorescence-imaging system.

Results: After radiolabeling procedures with Tc-99m, Tc-99m Folate-ECG-ROX complexes were prepared in high yield (> 97%). The binding affinity value (K) of Tc-99m Folate-ECG-ROX for KB cells was estimated to be 6.9 ± 0.9 nM. In gamma camera imaging, tumor to normal muscle uptake ratio of Tc-99m Folate-ECG-ROX increased with time (3.4 ± 0.4, 4.4 ± 0.7, and 6.6 ± 0.8 at 1, 2, and 3 h, respectively). In biodistribution study, %IA/g for KB tumor was 2.50 ± 0.80 and 4.08 ± 1.16 at 1 and 3 h, respectively. Confocal microscopy with immunohistochemistry staining detected strong Tc-99m Folate-ECG-ROX fluorescence within KB tumor tissue which is correlating with the fluorescent activity of anti-FR antibody. Under real-time optical imaging, the removal of visible nodules was successfully performed.

Conclusions: In vivo and in vitro studies revealed substantial and specific uptake of Tc-99m Folate-ECG-ROX in FR-positive tumors. Thus, Tc-99m Folate-ECG-ROX could provide both pre-operative molecular imaging and fluorescence image-guidance for tumor.
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http://dx.doi.org/10.1007/s12149-019-01369-2DOI Listing
August 2019

The usefulness of ultrasound and the posterior fat pad sign in pulled elbow.

Injury 2019 Jun 29;50(6):1227-1231. Epub 2019 Apr 29.

Department of Orthopedic Surgery, College of Medicine, Korea University, Seoul, Republic of Korea. Electronic address:

Introduction: A pulled elbow is a common cause of acute elbow pain that is generally managed by a reduction maneuver without radiographic examination. However, children with atypical presentation with no history of abrupt longitudinal traction should undergo elbow imaging. This study aimed to investigate plain radiography findings and determine the usefulness of ultrasonography (US) in atypical pulled elbow.

Materials And Methods: We retrospectively reviewed the medical records and images of 37 (22 males) consecutive patients with pulled elbow who presented with an atypical history or failed reduction between April 2015 and September 2018. Mean age at presentation was 4.34 years (range, 1.25-9.5 years). Of the 37 elbows, 20 were left elbows. The injury mechanism, incidence of the posterior fat pad sign on plain radiographs, and characteristic US findings, pre- and post- reduction, were investigated.

Results: The original mechanisms of injury included slipping (n = 14), rolling over the arm (n = 7), vague history (n = 6), falling down (n = 6), abrupt longitudinal traction (n = 2), and direct injury (n = 2). On plain radiographs, six of the 37 elbows (16%) showed the posterior fat pad sign. Before the reduction, an entrapped supinator, a pathognomonic sign of pulled elbow, was identified on US in all cases. After reduction, the characteristic US findings showed a disentangled and swollen supinator (100%) and restored annular ligament (100%) in all successful cases. Although a click was not felt in three cases, the reductions were considered successful because the annular ligament was restored on US with free elbow motion.

Conclusion: Pulled elbow may be caused by atypical mechanisms of injury, such as slipping and rolling over the arm. Clinicians should be aware of the possibility of the posterior fat pad sign on plain radiographs of pulled elbow to prevent unnecessary immobilization. In such circumstances, US is a useful method for detecting an entrapped supinator and confirming adequate reduction via restoration of the annular ligament in children with atypical pulled elbow.
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http://dx.doi.org/10.1016/j.injury.2019.04.026DOI Listing
June 2019

Radiographic prediction of lunate morphology in Asians using plain radiographic and capitate-triquetrum distance analyses: reliability and compatibility with magnetic resonance arthrography (MRA) findings.

BMC Musculoskelet Disord 2019 Mar 27;20(1):128. Epub 2019 Mar 27.

Department of Orthopaedic Surgery, Korea University Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, Sungbuk-gu, Seoul, 06334, South Korea.

Background: The purpose of this study was to examine the reliability of plain radiographic methods of determining the lunate type and its compatibility with magnetic resonance arthrography (MRA) findings.

Methods: Plain radiographs of a total of 150 wrists were reviewed by three observers. Lunate types were evaluated using both conventional posteroanterior (PA) radiographic analysis and the capitate-triquetrum distance (CTD) analysis. Cohen kappa and Fleiss kappa statistics were used to estimate intra- and inter-observer reliabilities. Compatibility with the MRA findings, as assessed by each observer, was investigated.

Results: The overall intra-observer reliability was 0.517 for the analysis and 0.589 for the CTD analysis. The overall inter-observer agreement was 0.448 for the PA radiographic analysis and 0.581 for the CTD analysis. The PA radiographic analysis and MRA findings for the detection of medial lunate facets were compatible in 119 of the 150 patients (79.3%). Twenty-eight (90.3%) of the 31 incompatible wrists had a medial facet on MRA (Type II), which was not detected in the PA radiographic analysis. In the CTD analysis, the results for 27 of 29 Type II lunates (93.1%) and 39 of 45 Type I lunates (86.7%) were compatible with the MRA.

Conclusions: This study suggests that predicting the lunate type by plain radiographs alone is insufficient, as both radiographic analyses showed moderate intra- and inter-observer reliabilities. Although both radiographic analyses showed good compatibility with the MRA for Type II lunates, clinicians should be alert to undetected medial facets in Type I lunates on PA radiographic analysis.
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http://dx.doi.org/10.1186/s12891-019-2483-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437918PMC
March 2019

Loss of SLC25A11 causes suppression of NSCLC and melanoma tumor formation.

EBioMedicine 2019 Feb 25;40:184-197. Epub 2019 Jan 25.

Tumor Microenvironment Research Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Republic of Korea. Electronic address:

Background: Fast growing cancer cells require greater amounts of ATP than normal cells. Although glycolysis was suggested as a source of anabolic metabolism based on lactate production, the main source of ATP to support cancer cell metabolism remains unidentified.

Methods: We have proposed that the oxoglutarate carrier SLC25A11 is important for ATP production in cancer by NADH transportation from the cytosol to mitochondria as a malate. We have examined not only changes of ATP and NADH but also changes of metabolites after SLC25A11 knock down in cancer cells.

Findings: The mitochondrial electron transport chain was functionally active in cancer cells. The cytosolic to mitochondrial NADH ratio was higher in non-small cell lung cancer (NSCLC) and melanoma cells than in normal cells. This was consistent with higher levels of the oxoglutarate carrier SLC25A11. Blocking malate transport by knockdown of SLC25A11 significantly impaired ATP production and inhibited the growth of cancer cells, which was not observed in normal cells. In in vivo experiments, heterozygote of SLC25A11 knock out mice suppressed KRAS lung tumor formation by cross breeding.

Interpretation: Cancer cells critically depended on the oxoglutarate carrier SLC25A11 for transporting NADH from cytosol to mitochondria as a malate form for the purpose of ATP production. Therefore blocking SLC25A11 may have an advantage in stopping cancer growth by reducing ATP production. FUND: The Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT to SYK (NRF-2017R1A2B2003428).
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http://dx.doi.org/10.1016/j.ebiom.2019.01.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413681PMC
February 2019

Renal Cell Carcinoma Is Abrogated by p53 Stabilization through Transglutaminase 2 Inhibition.

Cancers (Basel) 2018 Nov 19;10(11). Epub 2018 Nov 19.

Tumor Microenvironment Research Branch, Division of Cancer Biology, National Cancer Center, Goyang, Gyeonggi-do 10408, Korea.

In general, expression of transglutaminase 2 (TGase 2) is upregulated in renal cell carcinoma (RCC), resulting in p53 instability. Previous studies show that TGase 2 binds to p53 and transports it to the autophagosome. Knockdown or inhibition of TGase 2 in RCC induces p53-mediated apoptosis. Here, we screened a chemical library for TGase 2 inhibitors and identified streptonigrin as a potential therapeutic compound for RCC. Surface plasmon resonance and mass spectroscopy were used to measure streptonigrin binding to TGase 2. Mass spectrometry analysis revealed that streptonigrin binds to the N-terminus of TGase 2 (amino acids 95⁻116), which is associated with inhibition of TGase 2 activity in vitro and with p53 stabilization in RCC. The anti-cancer effects of streptonigrin on RCC cell lines were demonstrated in cell proliferation and cell death assays. In addition, a single dose of streptonigrin (0.2 mg/kg) showed marked anti-tumor effects in a preclinical RCC model by stabilizing p53. Inhibition of TGase 2 using streptonigrin increased p53 stability, which resulted in p53-mediated apoptosis of RCC. Thus, targeting TGase 2 may be a new therapeutic approach to RCC.
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http://dx.doi.org/10.3390/cancers10110455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267221PMC
November 2018

Tc-99m and Fluorescence-Labeled Anti-Flt1 Peptide as a Multimodal Tumor Imaging Agent Targeting Vascular Endothelial Growth Factor-Receptor 1.

Nucl Med Mol Imaging 2018 Oct 24;52(5):359-367. Epub 2018 Jul 24.

1Department of Nuclear Medicine and Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, 344-2 Shinyong-Dong, Iksan, Jeollabuk-do 570-711 Republic of Korea.

Purpose: We developed a Tc-99m and fluorescence-labeled peptide, Tc-99m TAMRA-GHEG-ECG-GNQWFI, to target tumor cells, and evaluated the diagnostic performance as a dual-modality imaging agent for tumor in a murine model.

Methods: TAMRA-GHEG-ECG-GNQWFI was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-GNQWFI with Tc-99m was done using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with U87MG tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry using confocal microscopy.

Results: After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-GNQWFI complexes were prepared in high yield (> 95%). The of Tc-99m TAMRA-GHEG-ECG-GNQWFI determined by saturation binding was 29.5 ± 4.5 nM. Confocal microscopy images of U87MG cells incubated with TAMRA-GHEG-ECG-GNQWFI showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI in tumors. Tumor uptake was effectively blocked by the co-injection of an excess concentration of GNQWFI. Specific uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI was assessed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies.

Conclusions: In vivo and in vitro studies revealed substantial and specific uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI in tumor cells. Tc-99m TAMRA-GHEG-ECG-GNQWFI could be a good candidate dual-modality imaging agent for tumors.
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http://dx.doi.org/10.1007/s13139-018-0535-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177343PMC
October 2018

FA Cs PbI (PF ) Interlayer Formed by Ion Exchange Reaction between Perovskite and Hole Transporting Layer for Improving Photovoltaic Performance and Stability.

Adv Mater 2018 Aug 23:e1801948. Epub 2018 Aug 23.

School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon, 440-746, South Korea.

Interface engineering to form an interlayer via ion exchange reaction is reported. A FA Cs PbI formamidinium (FA) perovskite layer is first prepared, then FAPF solution with different concentrations is spin-coated on top of the perovskite film, which leads to a partial substitution of iodide by PF ion. The second phase with nominal composition of FA Cs PbI (PF ) is grown at the grain boundary, which has island morphology and its size depends on the FAPF solution concentration. The lattice is expanded and bandgap is reduced due to inclusion of larger PF ions. The power conversion efficiency (PCE) is significantly enhanced from 17.8% to 19.3% as a consequence of improved fill factor and open-circuit voltage (V ). In addition, current-voltage hysteresis is reduced. Post-treatment with FAPF reduces defect density and enhances carrier lifetime, which is responsible for the improved photovoltaic performance and reduced hysteresis. The unencapsulated device with post-treated perovskite film demonstrates better stability than the pristine perovskite, where the initial PCE retains over 80% after 528 h exposure under relative humidity of around 50-70% in the dark and 92% after 360 h under one sun illumination.
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http://dx.doi.org/10.1002/adma.201801948DOI Listing
August 2018

Allosteric inhibition site of transglutaminase 2 is unveiled in the N terminus.

Amino Acids 2018 Nov 14;50(11):1583-1594. Epub 2018 Aug 14.

Tumor Microenvironment Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, 10408, Republic of Korea.

Previously we have demonstrated transglutaminase 2 (TGase 2) inhibition abrogated renal cell carcinoma (RCC) using GK921 (3-(phenylethynyl)-2-(2-(pyridin-2-yl)ethoxy)pyrido[3,2-b]pyrazine), although the mechanism of TGase 2 inhibition remains unsolved. Recently, we found that the increase of TGase 2 expression is required for p53 depletion in RCC by transporting the TGase 2 (1-139 a.a)-p53 complex to the autophagosome, through TGase 2 (472-687 a.a) binding p62. In this study, mass analysis revealed that GK921 bound to the N terminus of TGase 2 (81-116 a.a), which stabilized p53 by blocking TGase 2 binding. This suggests that RCC survival can be stopped by p53-induced cell death through blocking the p53-TGase 2 complex formation using GK921. Although GK921 does not bind to the active site of TGase 2, GK921 binding to the N terminus of TGase 2 also inactivated TGase 2 activity through acceleration of non-covalent self-polymerization of TGase 2 via conformational change. This suggests that TGase 2 has an allosteric binding site (81-116 a.a) which changes the conformation of TGase 2 enough to accelerate inactivation through self-polymer formation.
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http://dx.doi.org/10.1007/s00726-018-2635-2DOI Listing
November 2018

Rear-Surface Passivation by Melaminium Iodide Additive for Stable and Hysteresis-less Perovskite Solar Cells.

ACS Appl Mater Interfaces 2018 Aug 20;10(30):25372-25383. Epub 2018 Jul 20.

School of Chemical Engineering , Sungkyunkwan University (SKKU) , Suwon 440-746 , Korea.

Surface passivation of perovskite grains is one of the promising methods to reduce recombination and improve stability of perovskite solar cells (PSCs). We herein report the effect of a melaminium iodide additive on the photovoltaic performance of PSCs based on (FAPbI)(CsPbBr) perovskite. Cyclic -C═N- and primary amine in melamine are a good hydrogen bond acceptor and Lewis base, which can interact with both the organic cation and Lewis acidic lead iodide in the perovskite film. Melaminium iodide is synthesized and added to the precursor solution, which is directly spin-coated to form the perovskite film. The presence of melaminium iodide additive reduces the trap density from 1.02 × 10 to 0.645 × 10 cm, which leads to the reduction of nonradiative recombination and thereby improving the mean open-circuit voltage and the fill factor from 1.054 to 1.095 V and from 0.693 to 0.725 V, receptively. In addition, photocurrent-voltage hysteresis is reduced by the melaminium iodide additive, which results in an enhanced average power conversion efficiency, obtained from reverse and forward scanned data, from 15.86 to 17.32%. Time-resolved photoluminescence confirms that melaminium iodide plays a more important role in passivating the rear surface of the perovskite layer contacting the hole transporting spiro-MeOTAD layer. An aging test under a relative humidity of 65% reveals that melaminium iodide improves stability because of the suppression of the defect evolved by moisture.
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http://dx.doi.org/10.1021/acsami.8b06616DOI Listing
August 2018

All-Inorganic Bismuth Halide Perovskite-Like Materials ABiI and ABiNaI (A = Rb and Cs) for Low-Voltage Switching Resistive Memory.

ACS Appl Mater Interfaces 2018 Sep 22;10(35):29741-29749. Epub 2018 Aug 22.

School of Chemical Engineering , Sungkyunkwan University , Suwon 16419 , Korea.

As silicon-based metal oxide semiconductor field effect transistors get closer to their scaling limit, the importance of resistive random-access memory devices increases due to their low power consumption, high endurance and retention performance, scalability, and fast switching speed. In the last couple of years, organic-inorganic lead halide perovskites have been used for resistive switching applications, where they outperformed conventional metal oxides in terms of large on/off ratio and low power consumption. However, there were scarce reports on lead-free perovskites for such applications. In this report, we prepared lead-free Au/ABiI/Pt/Ti/SiO/Si (A is either Cs or Rb) devices and tested their resistive switching characteristics. They showed a forming step prior to repeating switching, low operating voltage (0.09 V for RbBiI and 0.1 V for CsBiI), large on/off ratio (>10), relatively high endurance (200 cycles for RbBiI and 400 cycles for CsBiI cycles), and high retention (1000 s). Such low voltage could be explained by grain boundary-modulated ion drift. Difference in endurance was speculated to be due to the difference in the surface roughness of films because CsBiI films are smoother. To get rid of the forming step, 10% of the Bi cations were substituted with Na cations. However, this method only worked on Rb-based structures. This phenomenon was explained by the defect formation energy, which can only be negative in a corner-sharing RbBiI structure compared to a face-sharing octahedral CsBiI structure. As a result, the forming step was removed, and 100 cycles endurance and 1000 s retention performance were obtained. Similarly, the lower endurance is suspected to be due to the poor surface quality of the film.
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http://dx.doi.org/10.1021/acsami.8b07103DOI Listing
September 2018
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