702 results on '"Lee YG"'
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2. 6-Metoxyflavonols from the aerial parts of Tetragonia tetragonioides (Pall.) Kuntze and their potential as anti-inflammatory agents
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Lee, YG, additional, Ryuk, JA, additional, Gwag, JE, additional, Hwang, JT, additional, Kim, HG, additional, Jung, EJ, additional, Chung, DK, additional, Lee, DS, additional, Ko, BS, additional, and Baek, NI, additional
- Published
- 2019
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3. Fibrin turnover and organization of pleural injury: Bench to bedside
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Komissarov, AA, Rahman, NM, Lee, YG, Florova, G, Shetty, S, Idell, R, Ikebe, M, Das, K, Tucker, TA, and Idell, S
- Abstract
Recent studies have shed new light on the role of the fibrinolytic system in the pathogenesis of pleural organization, including mechanisms by which the system regulates mesenchymal transition of mesothelial cells and how that process affects outcomes of pleural injury. The key contribution of plasminogen activator inhibitor-1 to the outcomes of pleural injury is now better understood as is its role in the regulation of intrapleural fibrinolytic therapy. In addition, mechanisms by which fibrinolysins are processed after intrapleural administration have now been elucidated, informing new candidate diagnostics and therapeutics for pleural loculation and failed drainage. The emergence of new potential interventional targets offers the potential for the development of new and more effective therapeutic candidates.
- Published
- 2018
4. Preparation and Characterization of Chlorine Doped Li3V2(PO4)3 as High Rate Cathode Active Material for Lithium Secondary Batteries
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Lee Sn, Kim Hs, Lee Yg, An Jy, S. Amaresh, Kyung-Wan Nam, and Yun-Sung Lee
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Materials science ,Lithium vanadium phosphate battery ,Inorganic chemistry ,Doping ,Biomedical Engineering ,chemistry.chemical_element ,Bioengineering ,Potassium-ion battery ,General Chemistry ,Electrolyte ,Condensed Matter Physics ,Cathode ,law.invention ,Anode ,chemistry ,law ,Chlorine ,General Materials Science ,Faraday efficiency - Abstract
Monoclinic Li3V2(PO4)2.99Cl0.01 was synthesized using the conventional solid state method and the X-ray diffraction pattern was indexed based on P2(1)/n space group. The sharp cyclic voltammetric curves clearly revealed three lithium extraction/insertion processes at approximately 3.64, 3.72, 4.13, and 4.58 V during the anodic scan and 3.96, 3.58, and 3.48 V during the cathodic scan. Charge/discharge studies showed reduced electrolyte decomposition contribution in the case of the chlorine doped Li3V2(PO4)2.99Cl0.01 sample with an initial capacity of 176 mA h g(-1) at a 0.1 C current rate. The chlorine doped Li3V2(PO4)3 sample showed an increased capacity retention with an increase in current rate, even at a very high C-rate (20 C), than the pristine and carbon coated samples. The pristine and carbon coated Li3V2(PO4)3 samples showed a lower capacity retention of 71% and 84%, respectively, at a current rate of 0.1 C. In contrast, the chlorine doped Li3V,(PO4)3 sample retained 87% of the initial capacity (176 mA h g(-1)) at the same current rate but with a higher coulombic efficiency of 91%. The enhanced capacity retention for the chlorine doped Li3V2(PO4)3 was attributed to the reduction in polarization and decreased charge transfer resistance of the electrode.
- Published
- 2014
5. Kinase activity-independent suppression of p73α by AMP-activated kinase α (AMPKα)
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Soo J. Um, Eun-Joo Kim, Lee Sw, Lee Yg, and Sin Hs
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Cancer Research ,Immunoprecipitation ,Kinase ,Transcription (biology) ,Genetics ,Phosphorylation ,Kinase activity ,Biology ,Protein kinase A ,Molecular Biology ,Chromatin immunoprecipitation ,Psychological repression ,Molecular biology - Abstract
Although p73alpha induces many of the same cellular events as p53, it is structurally distinct from p53 in that it possesses a unique COOH-terminal domain. To dissect the function of this domain, we performed yeast two-hybrid screening of a HeLa cDNA library using residues 552-636 of p73alpha as bait. Among the clones that showed a specific interaction with p73alpha was AMP-activated protein kinase alpha (AMPKalpha). Additional yeast two-hybrid assays indicated that the betagamma-binding domain of AMPKalpha is critical for the interaction with p73alpha. The interaction was further confirmed in vitro by glutathione S-transferase pull-down, and in vivo by immunoprecipitation and immunofluorescence microscopy. Transient coexpression of AMPKalpha resulted in downregulation of the effect of p73alpha, but not of p53, on various p53-responsive promoters. Chromatin immunoprecipitation indicated p73alpha-dependent recruitment of AMPKalpha to the p21WAF1 promoter. Treatment with 5-aminoimidazole-4-carboxamide ribonucleotide, an agonist of AMPKalpha, and expression of dominant-negative versions of AMPKalpha revealed that the repression of p73alpha was independent of AMPKalpha kinase activity. In addition, cisplatin-induced growth repression was impaired when AMPKalpha was overexpressed. Upon the knock down of AMPKalpha by siRNA, the induction of p21WAF1 by p73alpha was significantly increased. Taken together, these data indicate that AMPKalpha specifically regulates p73alpha by a direct interaction without affecting its phosphorylation status. From these data, we speculate that AMPKalpha may provide a molecular clue to understand the repressive role of the C-terminus of p73alpha in transcription and DNA damage response.
- Published
- 2008
6. 0301 ALTERED INTRINSIC FUNCTIONAL CONNECTIVITY OF FRONTOSTRIATAL REGIONS IN PATIENTS WITH PSYCHOPHYSIOLOGICAL INSOMNIA: A RESTING-STATE FMRI STUDY
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Kim, S, primary, Lee, YG, additional, Kim, N, additional, Choi, J, additional, Park, J, additional, Kim, S, additional, and Lee, Y, additional
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- 2017
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7. 0297 THE EFFECT OF COGNITIVE-BEHAVIORAL THERAPYON INTRINSIC FUNCTIONAL CONNECTIVITY IN PATIENTS WITH PSYCHOPHYSIOLOGICAL INSOMNIA: A RESTING STATE FMRI STUDY
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Lee, YG, primary, Kim, S, additional, Kim, N, additional, Choi, J, additional, Park, J, additional, and Lee, Y, additional
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- 2017
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8. Antihypertensive effects of ethanolic fruit extract of Acanthopanax sessiliflorus
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Choi, TJ, additional, Lee, DY, additional, Lee, YG, additional, Kim, GS, additional, Baek, NI, additional, and Jung, IH, additional
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- 2016
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9. Novel membrane bioreactor (MBR) coupled with a nonwoven fabric filter for household wastewater treatment
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Ren, X, Shon, HK, Jang, N, Lee, YG, Bae, M, Lee, J, Cho, K, Kim, IS, Ren, X, Shon, HK, Jang, N, Lee, YG, Bae, M, Lee, J, Cho, K, and Kim, IS
- Abstract
Conventional and modified membrane bioreactors (MBRs) are increasingly used in small-scale wastewater treatment. However, their widespread applications are hindered by their relatively high cost and operational complexity. In this study, we investigate a new concept of wastewater treatment using a nonwoven fabric filter bag (NFFB) as the membrane bioreactor. Activated sludge is charged in the nonwoven fabric filter bag and membrane filtration via the fabric is achieved under gravity flow without a suction pump. This study found that the biofilm layer formed inside the NFFB achieved 10 mg/L of suspended solids in the permeate within 20 min of initial operation. The dynamic biofilter layer showed good filterability and the specific membrane resistance consisted of 0.3-1.9 × 1012 m/kg. Due to the low F/M ratio (0.04-0.10 kg BOD5/m3/d) and the resultant low sludge yield, the reactor was operated without forming excess sludge. Although the reactor provided aerobic conditions, denitrification occurred in the biofilm layer to recover the alkalinity, thereby eliminating the need to supplement the alkalinity. This study indicates that the NFFB system provides a high potential of effective wastewater treatment with simple operation at reduced cost, and hence offer an attractive solution for widespread use in rural and sparsely populated areas. Crown Copyright © 2009.
- Published
- 2010
10. The Clinical Role and Reliability of Pleural Fluid Mesothelin in Undiagnosed Pleural Effusions.
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Davies, HE, primary, Sadler, RS, additional, Bielsa, S, additional, Maskell, NA, additional, Rahman, NM, additional, Davies, RJ, additional, Ferry, BL, additional, and Lee, YG, additional
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- 2009
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11. Comparison between Tonopachy and other tonometric and pachymetric devices.
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Lee YG, Kim JH, Kim NR, Kim CY, Lee ES, Lee, Yong Gi, Kim, Ji Hyun, Kim, Na Rae, Kim, Chan Yun, and Lee, Eun Suk
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- 2011
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12. Effects of human capital on the likelihood of working in later life.
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Lee YG and Brown SM
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- 2009
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13. Ginsenoside Rp1, a ginsenoside derivative, blocks lipopolysaccharide-induced interleukin-1ß production via suppression of the NF-kappaB pathway.
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Kim BH, Lee YG, Park TY, Kim HB, Rhee MH, and Cho JY
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- 2009
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14. Hinokitiol, a natural tropolone derivative, inhibits TNF-alpha production in LPS-activated macrophages via suppression of NF-kappaB.
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Byeon SE, Lee YG, Kim JC, Han JG, Lee HY, and Cho JY
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- 2008
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15. Microstructural Evaluation and Quantitative Analysis in the Unleaded Solder Joint.
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Bailey, GW, Jerome, WG, McKernan, S, Mansfield, JF, Price, RL, Duh, JG, Lee, YG, and Wu, FB
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- 1999
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16. Microstructural Evaluation and Quantitative Analysis in the Unleaded Solder Joint
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Duh, JG, Lee, YG, and Wu, FB
- Abstract
Solder joints provide mechanical and electronic connections between solders and components for various levels in microelectronic package. However, due to different thermal expansion coefficients and elastic modulus of the associated materials, solder joints are susceptible to fatigue degration, microcracks and fracture. The solder joint reliability is, therefore, critical in the evalution of the joint quality. Recently, the employment of lead-free solder is attractive due to the environmental concern of the Pb-containing solder. Hence, the investigation on the unleaded solder joint is of practical importance in the field of microelectronic package.Intermetallic compounds (IMC), which form and grow between solders and metallizations, are considered to be a source of mechanical weakness for its brittleness and different coefficient of thermal expansion from the metallization or the solder.
- Published
- 1999
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17. In vitro and in vivo anti-inflammatory effects of ethanol extract from Acer tegmentosum.
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Yu T, Lee J, Lee YG, Byeon SE, Kim MH, Sohn E, Lee YJ, Lee SG, and Cho JY
- Abstract
AIM OF STUDY: Acer tegmentosum has been traditionally used for folk medicine to treat hepatic disorders such as hepatitis, hepatic cancer, and hepatic cirrhosis. In this study, we demonstrate the ethno-pharmacological activity of Acer tegmentosum in in vitro and in vivo inflammatory conditions. RESULTS: The 70% ethanol extract (At-EE) of Acer tegmentosum dose-dependently diminished the production of nitric oxide (NO), tumour necrosis factor (TNF)-alpha, and prostaglandin (PG)E(2), in lipopolysaccharide (LPS)-activated RAW264.7 cells and peritoneal macrophages, by a transcriptional mechanism. At-EE also suppressed the activation of nuclear factor (NF)-kappaB, activator protein (AP)-1, and cAMP-responsive element binding (CREB), and simultaneously blocked their upstream inflammatory signalling cascades, including Akt, p38, and JNK. Furthermore, At-EE protected against LPS-induced cell death induced by reactive oxygen species (ROS) and reactive nitrogen species (RNS) and neutralized reactive species generation. In agreement with the in vitro results, orally administered At-EE strongly ameliorated ear oedema formation induced by arachidonic acid. CONCLUSION: At-EE displays strong anti-inflammatory activities in vitro and in vivo, contributing to its major ethno-pharmacological role such as anti-hepatitis remedy and may be applicable to novel anti-inflammatory therapeutics. [ABSTRACT FROM AUTHOR]
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- 2010
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18. CBL-b E3 ligase-mediated neddylation and activation of PARP-1 induce vascular calcification.
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Kwon DH, Shin S, Nam YS, Choe N, Lim Y, Jeong A, Lee YG, Kim YK, and Kook H
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Vascular calcification (VC) refers to the accumulation of mineral deposits on the walls of arteries and veins, and it is closely associated with increased mortality in cardiovascular disease patients, particularly among high-risk patients with diabetes and chronic kidney disease (CKD). Neuronal precursor cell-expressed developmentally downregulated protein 8 (NEDD8) is a ubiquitin-like protein that plays a pivotal role in various cellular functions, primarily through its conjugation to target proteins and subsequent relay of biological signals. However, the role of NEDDylation in VC has not been investigated. In our study, we observed that MLN4924, an inhibitor of the NEDD8-activating E1 enzyme, effectively impedes the progression of VC. LC‒MS/MS analysis revealed that poly(ADP‒ribose) polymerase 1 (PARP-1) is subjected to NEDD8 conjugation, leading to an increase in PARP-1 activity during VC. We subsequently revealed that PARP-1 NEDDylation is mediated by the E3 ligase CBL proto-oncogene B (CBL-b) and is reversed by NEDD8-specific protease 1 (NEDP-1) during VC. Furthermore, the CBL-b C373 peptide effectively mitigated the inactive form of the E3 ligase activity of CBL-b, ultimately preventing VC. These findings provide compelling evidence that the NEDD8-dependent activation of PARP-1 represents a novel mechanism underlying vascular calcification and suggests a promising new therapeutic target for VC., (© 2024. The Author(s).)
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- 2024
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19. Association between striatal amyloid deposition and motor prognosis in Parkinson's disease.
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Park M, Kim HJ, Baik K, Na HK, Lee YG, Yoon SH, Jeong SH, Chung SJ, Shin HW, Lyoo CH, Sohn YH, and Lee PH
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- Humans, Female, Male, Aged, Middle Aged, Retrospective Studies, Prognosis, Amyloid beta-Peptides metabolism, Levodopa therapeutic use, Levodopa adverse effects, Aniline Compounds, Stilbenes, Parkinson Disease metabolism, Parkinson Disease diagnostic imaging, Parkinson Disease complications, Positron-Emission Tomography, Corpus Striatum metabolism, Corpus Striatum diagnostic imaging
- Abstract
Background and Purpose: The co-occurrence of amyloid-β pathology in Parkinson's disease (PD) is common; however, the role of amyloid-β deposition in motor prognosis remains elusive. This study aimed to investigate the association between striatal amyloid deposition, motor complications and motor prognosis in patients with PD., Methods: Ninety-six patients with PD who underwent
18 F florbetaben (FBB) positron emission tomography were retrospectively assessed. The ratio of the striatum to global (STG) FBB uptake was obtained for each individual, and patients were allotted into low and high STG groups according to the median value. The effect of STG group on regional amyloid deposition, the occurrence of motor complications and longitudinal change in levodopa equivalent dose (LED) requirement were investigated after controlling for age, sex, LED and disease duration at FBB scan., Results: The high STG group was associated with lower cortical FBB uptake in the parietal, occipital and posterior cingulate cortices and higher striatal FBB uptake compared to the low STG group. Patients in the high STG group had a higher risk of developing wearing off and levodopa-induced dyskinesia than those in the low STG group, whereas the risk for freezing of gait was comparable between the two groups. The high STG group showed a more rapid increase in LED requirements over time than the low STG group., Conclusions: These findings suggest that relatively high striatal amyloid deposition is associated with poor motor outcomes in patients with PD., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)- Published
- 2024
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20. Nationwide precision oncology pilot study: KOrean Precision Medicine Networking Group Study of MOlecular profiling-guided therapy based on genomic alterations in advanced solid tumors (KOSMOS) KCSG AL-20-05.
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Kim TY, Kim SY, Kim JH, Jung HA, Choi YJ, Hwang IG, Cha Y, Lee GW, Lee YG, Kim TM, Lee SH, Lee S, Yun H, Choi YL, Yoon S, Han SW, Kim TY, Kim TW, Zang DY, and Kang JH
- Abstract
Background: Next-generation sequencing (NGS) has become widely available but molecular profiling-guided therapy (MGT) had not been well established in the real world due to lack of available therapies and expertise to match treatment. Our study was designed to test the feasibility of a nationwide platform of NGS-guided MGT recommended by a central molecular tumor board (cMTB) for metastatic solid tumors., Patients and Methods: Patients with advanced or metastatic solid tumors with available NGS results and without standard treatment were enrolled. The cMTB interpreted the patients' NGS reports and recommended the following: (i) investigational medicinal products (IMPs) approved in other indications; (ii) alternative treatments; (iii) clinical trials. The primary variables were the proportion of patients with actionable genomic alterations and those receiving MGT as per cMTB recommendations. Others included treatment duration (TD), overall response rate (ORR), disease control rate (DCR), and safety., Results: From February 2021 to February 2022, 193 cases [99 (51.3%) men; median age 58 years (range 24-88 years); median line of previous treatment 3 (range 0-9)] from 29 sites were enrolled for 60 cMTB sessions. The median time from case submission to cMTB discussion was 7 days (range 2-20 days), and to IMP treatment initiation was 28 days (range 14-90 days). Actionable genetic alterations were found in 145 patients (75.1%). A total of 89 (46.1%) patients received actual dosing of IMPs, and 10 (5.2%) were enrolled in cMTB-recommended clinical trials, achieving an MGT rate of 51.3%. ORR and DCR of IMPs were 10.1% and 72.5%, respectively. The median TD was 3.5 months [95% confidence interval (CI) 2.8-5.5 months], and the 4-month TD rate was 44.9%. The median overall survival of patients who received IMPs was 6.9 months (95% CI 5.2-10.0 months)., Conclusion: KOSMOS confirmed the feasibility of MGT recommended by the cMTB, achieving a high MGT match rate and promising effectiveness in heavily pretreated advanced cancer patients., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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21. Licochalcone D from Glycyrrhiza uralensis Improves High-Glucose-Induced Insulin Resistance in Hepatocytes.
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Lee YG, Lee HM, Hwang JT, and Choi HK
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- Animals, Mice, Plant Extracts pharmacology, Plant Extracts chemistry, Signal Transduction drug effects, Cell Line, Insulin Resistance, Glycyrrhiza uralensis chemistry, Hepatocytes drug effects, Hepatocytes metabolism, Glucose metabolism, Chalcones pharmacology
- Abstract
This study investigated the therapeutic potential of licochalcone D (LicoD), which is derived from Glycyrrhiza uralensis , for improving glucose metabolism in AML12 hepatocytes with high-glucose-induced insulin resistance (IR). Ultra-high-performance liquid chromatography-mass spectrometry revealed that the LicoD content of G. uralensis was 8.61 µg/100 mg in the ethanol extract (GUE) and 0.85 µg/100 mg in the hot water extract. GUE and LicoD enhanced glucose consumption and uptake, as well as Glut2 mRNA expression, in high-glucose-induced IR AML12 cells. These effects were associated with the activation of the insulin receptor substrate/phosphatidylinositol-3 kinase signaling pathway, increased protein kinase B α phosphorylation, and suppression of gluconeogenesis-related genes, such as Pepck and G6pase . Furthermore, GUE and LicoD promoted glycogen synthesis by downregulating glycogen phosphorylase. Furthermore, LicoD and GUE mitigated the downregulated expression of mitochondrial oxidative phosphorylation proteins in IR hepatocytes by activating the PPARα/PGC1α pathway and increasing the mitochondrial DNA content. These findings demonstrate the potential of LicoD and GUE as therapeutic options for alleviating IR-induced metabolic disorders by improving glucose metabolism and mitochondrial function.
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- 2024
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22. Deciphering chemical diversity among five variants of Abeliophyllum distichum flowers through metabolomics analysis.
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Lee YG, Kwon JE, Choi WS, Baek NI, and Kang SC
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Abeliophyllum distichum (Oleaceae), endemic to the Korean Peninsula and the sole member of its genus and species, possesses high scarcity value, escalating its importance under the Nagoya Protocol. Despite its significance, their metabolites and activities of A. distichum flowers remain unexplored. This study employs an integrated metabolomic approach utilizing NMR, LC/MS, GC/MS, and FTIR techniques to comprehensively analyze the metabolite profile of A. distichum flowers. By combining these methods, we identified 35 metabolites, 43 secondary metabolites, and 108 hydrophobic primary metabolites. Notably, distinct concentration patterns of these compounds were observed across five variants, classified based on morphological characteristics. Correlation analyses of primary and secondary metabolites unveiled varietal metabolic flux, providing insights into A. distichum flower metabolism. Additionally, the reconstruction of metabolic pathways based on dissimilarities in morphological traits elucidates variant-specific metabolic signatures. These findings not only enhance our understanding of chemical differences between varieties but also underscore the importance of considering varietal differences in future research and conservation efforts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 The Author(s). Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)
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- 2024
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23. Earlier sexual debut as a risk factor for substance use among men who have sex with men (MSM) in Kazakhstan.
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Laughney CI, Lee YG, Mergenova G, Vinogradov V, Zhakupova G, Paine EA, Primbetova S, Terlikbayeva A, and Wu E
- Abstract
Background: Limited research have examined predictors of illicit use of drugs and binge drinking among gay, bisexual, and other men who have sex with men (MSM) in Kazakhstan and Central Asia. This study examines earlier sexual debut as a risk factor for lifetime and recent substance use behaviors among MSM in Kazakhstan., Methods: We conducted a secondary analysis of self-reported data from a NIDA-funded HIV prevention trial including 902 adult cisgender MSM in Kazakhstan who completed structured screening interviews. Logistic regression models were used to estimate associations between earlier sexual debut (ages 16 and older as the reference group) and lifetime and recent substance use, with covariance adjustment for sociodemographic characteristics., Results: The majority of MSM in our sample reported lifetime binge drinking behavior (73%) and illicit use of drugs (65%). Participants with an earlier sexual debut before 13 years old had significantly higher odds of lifetime binge drinking and any illicit use of drugs ( aOR = 2.3, 95%CI: 1.2-4.5; aOR =3.0, 95%CI: 1.6-5.8). MSM who reported an earlier sexual debut between 13-15 years old had significantly higher odds of lifetime binge drinking and illicit use of any drugs ( aOR =1.6, 95%CI: 1.1-2.3; aOR =1.6, 95%CI: 1.1-2.3); as well as recent binge drinking behavior ( aOR =1.6, 95%CI: 1.2-2.3)., Conclusion: Future research should examine pathways between earlier sexual experiences and substance use behaviors among sexually diverse populations. Earlier sexual experiences during childhood and adolescence may be relevant contextual information for interventions aimed at substance use risk prevention, treatment, and recovery among MSM populations., Competing Interests: Competing Interests The authors declare no competing interests.
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- 2024
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24. Development of New Diffuse Large B Cell Lymphoma Mouse Models.
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Mehdi SH, Xu YZ, Shultz LD, Kim E, Lee YG, Kendrick S, and Yoon D
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Diffuse large B cell lymphoma (DLBCL) is the most diagnosed, aggressive non-Hodgkin lymphoma, with ~40% of patients experiencing refractory or relapsed disease. Given the low response rates to current therapy, alternative treatment strategies are necessary to improve patient outcomes. Here, we sought to develop an easily accessible new xenograft mouse model that better recapitulates the human disease for preclinical studies. We generated two Luciferase (Luc)-EGFP-expressing human DLBCL cell lines representing the different DLBCL cell-of-origin subtypes. After intravenous injection of these cells into humanized NSG mice, we monitored the tumor growth and evaluated the organ-specific engraftment/progression period. Our results showed that human IL6-expressing NSG (NSG-IL6) mice were highly permissive for DLBCL cell growth. In NSG-IL6 mice, systemic engraftments of both U2932 activated B cell-like- and VAL germinal B cell-like-DLBCL (engraftment rate; 75% and 82%, respectively) were detected within 2nd-week post-injection. In the organ-specific ex vivo evaluation, both U2932- Luc and VAL- Luc cells were initially engrafted and expanded in the spleen, liver, and lung and subsequently in the skeleton, ovary, and brain. Consistent with the dual BCL2 / MYC translocation association with poor patient outcomes, VAL cells showed heightened proliferation in human IL6-conditioned media and caused rapid tumor expansion and early death in the engrafted mice. We concluded that the U2932 and VAL cell-derived human IL6-expressing mouse models reproduced the clinical features of an aggressive DLBCL with a highly consistent pattern of tumor development. Based on these findings, NSG mice expressing human IL6 have the potential to serve as a new tool to develop DLBCL xenograft models to overcome the limitations of standard subcutaneous DLBCL xenografts.
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- 2024
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25. Post-calcination as an effective approach to enhance adsorption of arsenic and antimony anions by Mg/Al layered double hydroxide-decorated spent coffee ground biochars: Role of charge properties and active sites.
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Shin J, Lee SH, Kwak J, Son C, Kim S, Lee YG, Kim HJ, Rho H, Park Y, and Chon K
- Abstract
This study evaluated the effects of post-calcination on the charge properties and active sites of Mg/Al layered double hydroxide-decorated spent coffee ground biochars (LDH
MgAl @SCGB) governing adsorption behaviors and mechanisms of arsenic (AsV ) and antimony (SbV ) anions from aqueous phases. Post-calcinated LDHMgAl @SCGB (PLDHMgAl @SCGB) exhibited higher adsorption capacities for AsV and SbV compared to spent coffee ground biochars (SCGB) and LDHMgAl @SCGB as post-calcination of LDHMgAl @SCGB enhanced the charge properties (surface zeta potential at pH 7.0: SCGB = -21.8 mV, LDHMgAl @SCGB = 28.5 mV, and PLDHMgAl @SCGB = 34.4 mV) and increased active sites by eliminating the anions (i.e., Cl- ions) and water molecules at its interlayers. The calculated kinetic, intra-particle diffusion, and isotherm parameters indicated that the chemisorption and intra-particle diffusion were mainly responsible for the adsorption of AsV and SbV by SCGB, LDHMgAl @SCGB, and PLDHMgAl @SCGB. Moreover, post-calcination of LDHMgAl @SCGB enhanced its selectivity toward AsV and SbV by reinforcing the electrostatic surface complexation via its improvement of charge properties. Since PLDHMgAl @SCGB exhibited the excellent reusability for the adsorption of AsV (reuse efficiency > 63.6%) and SbV (reuse efficiency > 52.1%), it can be concluded that post-calcination of LDHMgAl @SCGB is a promising method for improving the adsorption capacities for AsV and SbV in real water matrices., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024. Published by Elsevier Ltd.)- Published
- 2024
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26. Post-diagnosis smoking habit change and incident dementia in cancer survivors.
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Lee HH, Ahn J, Jiang C, Lee YG, Kim HC, and Lee H
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Introduction: Many individuals change their smoking habits after cancer diagnosis. We aimed to evaluate the association of post-diagnosis smoking habit change with incident dementia in cancer survivors., Methods: We identified 558,127 individuals who were diagnosed with cancer at age ≥ 20 and survived for ≥ 3 years. Participants were classified into four groups: (1) sustained non-smokers, (2) initiators/relapsers, (3) quitters, and (4) continuing smokers. Dementia risk in each group was assessed using a cause-specific Cox model., Results: After cancer diagnosis, 2.3% of pre-diagnosis non-smokers initiated/relapsed into smoking, while 51.7% of pre-diagnosis smokers quit smoking. Compared to sustained non-smokers, multivariable-adjusted risk of dementia was 29% higher among initiators/relapsers, 11% higher among quitters, and 31% higher among continuing smokers. Compared to continuing smokers, the risk was 15% lower among quitters., Discussion: In cancer survivors, smoking initiation/relapse was associated with increased risk of dementia, whereas smoking cessation was associated with decreased risk of dementia., Highlights: Approximately half of pre-diagnosis smokers quit smoking after a cancer diagnosis. Smoking cessation was associated with a 15% reduced risk of dementia. More than 2% of pre-diagnosis non-smokers initiated or relapsed into smoking after a cancer diagnosis. Smoking initiation/relapse was associated with a 29% elevated risk of dementia., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
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- 2024
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27. Increasing HIV Testing Among Sexual and Gender Expansive Men in Kazakhstan: A Stepped-Wedge Randomized Trial of a Community-Level Intervention.
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Wu E, Lee YG, Vinogradov V, Zhakupova G, Mergenova G, Davis A, Paine EA, Hunt T, Reeder K, Primbetova S, Terlikbayeva A, Laughney C, Chang M, Baiserkin B, Abishev A, Tukeyev M, Abdraimov S, Denebayeva A, Kasymbekova S, Tazhibayeva G, and Kozhakhmet M
- Abstract
Importance: HIV transmission in Kazakhstan has increased among men who have sex with men (MSM) and transgender and nonbinary people who have sex with men (TSM), driven by low HIV testing rates., Objective: To determine if the PRIDE in HIV Care intervention had a community effect of increasing HIV testing among MSM and TSM in Kazakhstan., Design: We employed a stepped-wedge, cluster-randomized controlled trial with MSM and TSM community members recruited from three cities in Kazakhstan: Almaty, Astana, and Shymkent. We collected serial cross-sectional data where community members completed one assessment between 21 August 2018, and 30 March 2022., Setting: We collected data from 629 MSM and TSM among the study cities. Community respondents were recruited from real-world (e.g., NGOs, bars, clubs) or virtual sites (e.g., social media, apps) where MSM and TSM in each of the three cities were known to frequent., Participants: Eligibility criteria for community respondents were: (1) ≥18 years old; (2) identifying as male at any point in life or being assigned male at birth; (3) having consensual sex with another man in the past 12 months; (4) engaging in binge drinking (i.e., ≥5 drinks in a 2 hour period), illicit use of drugs, or both in the past 90 days; and (5) residing in one of the three study cities., Intervention: The PRIDE in HIV Care intervention is a theory-driven "crowdsourcing and peer-actuated network intervention" designed to amplify community members' successes and resilience via "influencers" who can strengthen and impart benefit to their networks and community., Main Outcome Measures: Received an HIV test in the prior six months., Results: There was a statistically significant increase in odds of recent HIV testing for every additional month the intervention was implemented in a respondent's city ( AOR =1.08, 95% CI =1.05-1.12; p <.001)., Conclusions: The PRIDE in HIV Care intervention appears to be efficacious in enacting a community wide increase-i.e., promoted HIV testing among those who did not go through the intervention itself-in HIV testing among MSM and TSM., Trial Registration: This trial is registered with clinicaltrials.gov (NCT02786615)., Funding: National Institute on Drug Abuse (NIDA), grant number R01DA040513., Competing Interests: Declaration of Interests We declare no competing interests.
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- 2024
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28. Zingiber officinale promotes autophagy and apoptosis in human oral cancer through the C/EBP homologous protein.
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Kim HJ, Shin JA, Lee YG, Jin B, Lee WW, Lee Y, Choi SJ, Han JM, Ahn MH, Kim JH, Park DG, Hong SD, Kang SC, and Cho SD
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- Humans, Cell Line, Tumor, Animals, Catechols pharmacology, Mice, Rhizome chemistry, Xenograft Model Antitumor Assays, Antineoplastic Agents, Phytogenic pharmacology, Zingiber officinale chemistry, Autophagy drug effects, Apoptosis drug effects, Transcription Factor CHOP metabolism, Mouth Neoplasms drug therapy, Mouth Neoplasms pathology, Mouth Neoplasms metabolism, Reactive Oxygen Species metabolism, Plant Extracts pharmacology, Endoplasmic Reticulum Stress drug effects
- Abstract
The rhizome of Zingiber officinale (Z. officinale), commonly known as ginger, has been characterized as a potential drug candidate due to its antitumor effects. However, the chemotherapeutic effect of ginger on human oral cancer remains poorly understood. In this study, we examined the effects of an ethanol extract of Z. officinale rhizomes (ZOE) on oral cancer and identified the components responsible for its pharmacological activity. ZOE exerts its inhibitory activity in oral cancer by inducing both autophagy and apoptosis simultaneously. Mechanistically, ZOE-induced autophagy and apoptosis in oral cancer are attributed to the reactive oxygen species (ROS)-mediated endoplasmic reticulum stress response. Additionally, we identified two active components of ZOE, 1-dehydro-6-gingerdione and 8-shogaol, which were sufficient to stimulate autophagy initiation and apoptosis induction by enhancing CHOP expression. These results suggest that ZOE and its two active components induce ROS generation, upregulate CHOP, initiate autophagy and apoptosis, and hold promising therapeutics against human oral cancer., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
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- 2024
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29. Cancer therapy-related cardiac dysfunction and the role of cardiovascular imaging: systemic review and opinion paper from the Working Group on Cardio-Oncology of the Korean Society of Cardiology.
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Cho I, You SC, Cha MJ, Hwang HJ, Cho EJ, Kim HJ, Park SM, Kim SE, Lee YG, Youn JC, Park CS, Shim CY, Chung WB, and Sohn IS
- Abstract
Cardio-oncology is a critical field due to the escalating significance of cardiovascular toxicity as a side effect of anticancer treatments. Cancer therapy-related cardiac dysfunction (CTRCD) is a prevalent condition associated with cardiovascular toxicity, necessitating effective strategies for prediction, monitoring, management, and tracking. This comprehensive review examines the definition and risk stratification of CTRCD, explores monitoring approaches during anticancer therapy, and highlights specific cardiovascular toxicities linked to various cancer treatments. These include anthracyclines, HER2-targeted agents, vascular endothelial growth factor inhibitors, immune checkpoint inhibitors, chimeric antigen receptor T-cell therapies, and tumor-infiltrating lymphocytes therapies. Incorporating the Korean data, this review offers insights into the regional nuances in managing CTRCD. Using systematic follow-up incorporating cardiovascular imaging and biomarkers, a better understanding and management of CTRCD can be achieved, optimizing the cardiovascular health of both cancer patients and survivors., (© 2024. The Author(s).)
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- 2024
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30. CD5 deletion enhances the antitumor activity of adoptive T cell therapies.
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Patel RP, Ghilardi G, Zhang Y, Chiang YH, Xie W, Guruprasad P, Kim KH, Chun I, Angelos MG, Pajarillo R, Hong SJ, Lee YG, Shestova O, Shaw C, Cohen I, Gupta A, Vu T, Qian D, Yang S, Nimmagadda A, Snook AE, Siciliano N, Rotolo A, Inamdar A, Harris J, Ugwuanyi O, Wang M, Carturan A, Paruzzo L, Chen L, Ballard HJ, Blanchard T, Xu C, Abdel-Mohsen M, Gabunia K, Wysocka M, Linette GP, Carreno B, Barrett DM, Teachey DT, Posey AD, Powell DJ Jr, Sauter CT, Pileri S, Pillai V, Scholler J, Rook AH, Schuster SJ, Barta SK, Porazzi P, and Ruella M
- Subjects
- Animals, Mice, Humans, Receptors, Chimeric Antigen immunology, Receptors, Chimeric Antigen genetics, Cell Line, Tumor, CRISPR-Cas Systems, Female, Immunotherapy, Adoptive methods, CD5 Antigens immunology, T-Lymphocytes immunology, T-Lymphocytes transplantation
- Abstract
Most patients treated with US Food and Drug Administration (FDA)-approved chimeric antigen receptor (CAR) T cells eventually experience disease progression. Furthermore, CAR T cells have not been curative against solid cancers and several hematological malignancies such as T cell lymphomas, which have very poor prognoses. One of the main barriers to the clinical success of adoptive T cell immunotherapies is CAR T cell dysfunction and lack of expansion and/or persistence after infusion. In this study, we found that CD5 inhibits CAR T cell activation and that knockout (KO) of CD5 using CRISPR-Cas9 enhances the antitumor effect of CAR T cells in multiple hematological and solid cancer models. Mechanistically, CD5 KO drives increased T cell effector function with enhanced cytotoxicity, in vivo expansion, and persistence, without apparent toxicity in preclinical models. These findings indicate that CD5 is a critical inhibitor of T cell function and a potential clinical target for enhancing T cell therapies.
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- 2024
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31. The therapeutic effects of vitamin D3 administration on the embryo implantation.
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Lee YG, Lee D, Cha H, Ahn J, Koo HS, Hwang SY, Lee G, and Kang YJ
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- Female, Pregnancy, Humans, Animals, Endometrium drug effects, Fertilization in Vitro methods, Embryo Transfer, Killer Cells, Natural drug effects, Neovascularization, Physiologic drug effects, Uterus drug effects, Embryo Implantation drug effects, Cholecalciferol pharmacology, Cholecalciferol administration & dosage
- Abstract
Various adjuvants have been tested clinically for patients with problems with embryo implantation during in vitro fertilization (IVF)-embryo transfer (ET). Vitamin D3, an essential modulator of various physiological processes, has received attention as an important adjuvant for successful pregnancy, as many studies have shown a strong association between vitamin D deficiency and implantation failure and fetal growth restriction. However, vitamin D has been widely utilized in different protocols, resulting in non-reproducible and debatable outcomes. In the present study, we demonstrated that cyclic intrauterine administration of vitamin D3 increased endometrial receptivity and angiogenesis, which could be attributed to increased recruitment of uterus-resident natural killer cells. In particular, cyclic treatment of vitamin D3 promoted stable attachment of the embryo onto endometrial cells in vitro, suggesting its merit during the early stage of embryo implantation to support the initial maternal-fetal interactions. Our findings suggest that women with repeated implantation failure may benefit from the use of vitamin D3 as a risk-free adjuvant prior to IVF-ET procedures to improve the uterine environment, and make it favorable for embryo implantation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
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- 2024
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32. MG53 mitigates warm ischemic lung injury in a murine model of transplantation.
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Gouchoe DA, Yi T, Kim JL, Lee YG, Black SM, Breuer C, Ma J, and Whitson BA
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- Animals, Mice, Knockout, Mice, Inbred C57BL, Mice, Lung metabolism, Lung pathology, Male, Tissue Plasminogen Activator genetics, Tissue Plasminogen Activator metabolism, Lung Injury prevention & control, Lung Injury metabolism, Lung Injury etiology, Lung Injury pathology, Lung Transplantation adverse effects, Lung Transplantation methods, Reperfusion Injury prevention & control, Reperfusion Injury metabolism, Reperfusion Injury etiology, Reperfusion Injury pathology, Warm Ischemia adverse effects, Disease Models, Animal
- Abstract
Objectives: Lung transplant warm ischemia-reperfusion injury (IRI) results in cellular injury, inflammation, and poor graft function. Mitsugumin 53 (MG53) is an endogenous protein with cell membrane repair properties and the ability to modulate the inflammasome. We hypothesize that the absence of circulating MG53 protein in the recipient increases IRI, and higher levels of circulating MG53 protein mitigate IRI associated with lung transplantation., Methods: To demonstrate protection, wild-type (wt) lung donor allografts were transplanted into a wt background, a MG53 knockout (mg53-/-), or a constitutively overexpressed MG53 (tissue plasminogen activator-MG53) recipient mouse after 1 hour of warm ischemic injury. Mice survived for 5 days after transplantation. Bronchioalveolar lavage, serum, and tissue were collected at sacrifice. Bronchioalveolar lavage, serum, and tissue markers of apoptosis and a biometric profile of lung health were analyzed., Results: mg53-/- mice had significantly greater levels of markers of overall cell lysis and endothelial cell injury. Overexpression of MG53 resulted in a signature similar to that of wt controls. At the time of explant, tissue plasminogen activator-MG53 recipient tissue expressed significantly greater levels of MG53, measured by immunohistochemistry, compared with mg53-/-, demonstrating uptake of endogenous overexpressed MG53 into donor tissue., Conclusions: In a warm IRI model of lung transplantation, the absence of MG53 resulted in increased cell injury and inflammation. Endogenous overexpression of MG53 in the recipient results in protection in the wt donor. Together, these data suggest that MG53 is a potential therapeutic agent for use in lung transplantation to mitigate IRI., Competing Interests: Conflict of Interest Statement J.M. is a founder of TRIM-edicine, Inc, a university spin-off biotechnology company that develops MG53 for regenerative medicine application. B.A.W. serves on the Clinical Events Committee of TransMedics OCS. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)
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- 2024
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33. A phase 2 study of spartalizumab (PDR001) among patients with recurrent or metastatic esophageal squamous cell carcinoma (KCSG HN18-17, K-MASTER project 12).
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Lee DK, Park SR, Kim YH, Lee YG, Shin SJ, Ahn BC, Lee SS, Lim SM, Kim HR, Cho BC, and Hong MH
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- Humans, Male, Female, Middle Aged, Aged, Adult, Progression-Free Survival, Aged, 80 and over, Programmed Cell Death 1 Receptor antagonists & inhibitors, Esophageal Squamous Cell Carcinoma drug therapy, Esophageal Squamous Cell Carcinoma pathology, Esophageal Squamous Cell Carcinoma mortality, Esophageal Neoplasms drug therapy, Esophageal Neoplasms pathology, Esophageal Neoplasms mortality, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized administration & dosage, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local pathology
- Abstract
Spartalizumab (PDR001) is a humanized IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1). We conducted a single-arm, phase 2 trial to investigate the efficacy and safety of spartalizumab in patients with refractory esophageal squamous cell carcinoma (ESCC). Patients with histologically confirmed ESCC who experienced disease progression after platinum-based chemotherapy received 300 mg of intravenous spartalizumab every three weeks until disease progression or occurrence of unacceptable toxicity. The primary endpoint was centrally assessed objective response according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Adverse events were closely monitored throughout the study. From March 2020 through April 2021, 44 patients with ESCC were enrolled. Of the 44 patients, the objective response rate was 20.5% (95% confidence interval: 8.5-32.4). With a median follow-up of 10.9 months, median progression-free survival and overall survival were 3.2 months and 11.2 months, respectively. In addition, the median duration of response was 24.7 months. The most common grade 3 or 4 adverse event was grade 3 dysphagia (eight [18%] patients). Biomarker analyses explored programmed cell death ligand 1 and CD20 as potential predictive markers for PD-1 blockade. Spartalizumab showed promising activity with a manageable safety profile, indicating its potential as a new treatment option for patients with refractory ESCC., Trial Registration: The trial was registered at ClinicalTrials.gov under the identifier NCT03785496., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)
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- 2024
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34. Exploring Alternative Perfusion Solutions Using Next-Generation Polymerized Hemoglobin-Based Oxygen Carriers in a Model of Rat Ex Vivo Lung Perfusion.
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Gouchoe DA, Lee YG, Greenfield A, Cuddington C, Kim JL, Black SM, Palmer AF, and Whitson BA
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- Animals, Rats, Humans, Oxygen metabolism, Blood Substitutes pharmacology, Blood Substitutes chemistry, Male, Organ Preservation Solutions chemistry, Lung Transplantation methods, Hemoglobins chemistry, Perfusion methods, Lung metabolism
- Abstract
Lung transplantation is hampered by the lack of suitable donors. Previously, donors that were thought to be marginal or inadequate were discarded. However, new and exciting technology, such as ex vivo lung perfusion (EVLP), offers lung transplant providers extended assessment for marginal donor allografts. This dynamic assessment platform has led to an increase in lung transplantation and has allowed providers to use donors that were previously discarded, thus expanding the donor pool. Current perfusion techniques use cellular or acellular perfusates, and both have distinct advantages and disadvantages. Perfusion composition is critical to maintaining a homeostatic environment, providing adequate metabolic support, decreasing inflammation and cellular death, and ultimately improving organ function. Perfusion solutions must contain sufficient protein concentration to maintain appropriate oncotic pressure. However, current perfusion solutions often lead to fluid extravasation through the pulmonary endothelium, resulting in inadvertent pulmonary edema and damage. Thus, it is necessary to develop novel perfusion solutions that prevent excessive damage while maintaining proper cellular homeostasis. Here, we describe the application of a polymerized human hemoglobin (PolyhHb)-based oxygen carrier as a perfusate and the protocol in which this perfusion solution can be tested in a model of rat EVLP. The goal of this study is to provide the lung transplant community with key information in designing and developing novel perfusion solutions, as well as the proper protocols to test them in clinically relevant translational transplant models.
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- 2024
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35. Posttraumatic stress disorder mediating associations between child sexual abuse and substance use among transgender adults in the United States.
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Laughney CI, Lee YG, Paine EA, and Wu E
- Abstract
Transgender people experience an excess burden of child sexual abuse (CSA), mental health concerns, and substance use compared to cisgender populations. Posttraumatic stress disorder (PTSD) has been found to mediate the association between CSA and substance use behaviors in cisgender populations, but this dynamic has not been previously examined among transgender adults. The aim of this study is to test if PTSD may mediate a relationship between CSA and substance use among transgender adults. Data were analyzed from the U.S. Transgender Population Health Survey (2016-2018), a national probability sample of transgender adults ( N = 274). CSA was measured using the Adverse Childhood Experiences subsection for sexual abuse. Past-month PTSD was measured using the Primary Care-PTSD Diagnostic and Statistical Manual of Mental Disorders, fourth edition screening tool. Substance use was determined by lifetime binge drinking, polydrug use, and the Drug Use Disorders Identification Test. Baron and Kenny's approach was used to assess PTSD as a mediator between CSA and substance use. Within our sample, nearly half (45%) of the transgender adults experienced CSA. Lifetime binge drinking (40%), polydrug use (20%), and indications of drug-use-related problems (Drug Use Disorders Identification Test x¯ = 4.52) were frequently reported. Transgender adults who have experienced CSA had increased risk of PTSD and substance use, and PTSD was a mediator in all models. Results suggest that adult transgender CSA survivors are at increased risk of drug and alcohol use, and that PTSD may be an important contextual factor for substance use. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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- 2024
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36. Evaluation of a Virtual Culturally Aware Mentoring Workshop for Biomedical Faculty.
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House SC, Byars-Winston A, Eiring E, Hurtado S, Lee YG, and McGee R
- Abstract
The Culturally Aware Mentoring (CAM) workshop was developed to help biomedical faculty gain awareness and skills to work more effectively with racially and ethnically minoritized mentees. The purpose of this paper is to present evaluation findings from a national cluster randomized comparative study in which CAM was delivered in an online format. We evaluated data from the primary arm of this study, which included 231 biomedical faculty from 12 universities. Overall, participants evaluated both the presentation and content of the online interactive intervention favorably, reporting it helped them become a more culturally aware mentor. They further suggested how the workshop may be improved. We discuss implications for mentorship practitioners and future research directions.
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- 2024
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37. The BTLA-HVEM axis restricts CAR T cell efficacy in cancer.
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Guruprasad P, Carturan A, Zhang Y, Cho JH, Kumashie KG, Patel RP, Kim KH, Lee JS, Lee Y, Kim JH, Chung J, Joshi A, Cohen I, Shestov M, Ghilardi G, Harris J, Pajarillo R, Angelos M, Lee YG, Liu S, Rodriguez J, Wang M, Ballard HJ, Gupta A, Ugwuanyi OH, Hong SJA, Bochi-Layec AC, Sauter CT, Chen L, Paruzzo L, Kammerman S, Shestova O, Liu D, Vella LA, Schuster SJ, Svoboda J, Porazzi P, and Ruella M
- Subjects
- Animals, Humans, Mice, Cell Line, Tumor, Mice, Knockout, Neoplasms immunology, Neoplasms therapy, Signal Transduction, T-Lymphocytes, Regulatory immunology, Immunotherapy, Adoptive methods, Receptors, Chimeric Antigen immunology, Receptors, Chimeric Antigen metabolism, Receptors, Chimeric Antigen genetics, Receptors, Immunologic metabolism, Receptors, Immunologic genetics, Receptors, Tumor Necrosis Factor, Member 14 metabolism, Receptors, Tumor Necrosis Factor, Member 14 immunology, Receptors, Tumor Necrosis Factor, Member 14 genetics, Tumor Microenvironment immunology
- Abstract
The efficacy of T cell-based immunotherapies is limited by immunosuppressive pressures in the tumor microenvironment. Here we show a predominant role for the interaction between BTLA on effector T cells and HVEM (TNFRSF14) on immunosuppressive tumor microenvironment cells, namely regulatory T cells. High BTLA expression in chimeric antigen receptor (CAR) T cells correlated with poor clinical response to treatment. Therefore, we deleted BTLA in CAR T cells and show improved tumor control and persistence in models of lymphoma and solid malignancies. Mechanistically, BTLA inhibits CAR T cells via recruitment of tyrosine phosphatases SHP-1 and SHP-2, upon trans engagement with HVEM. BTLA knockout thus promotes CAR signaling and subsequently enhances effector function. Overall, these data indicate that the BTLA-HVEM axis is a crucial immune checkpoint in CAR T cell immunotherapy and warrants the use of strategies to overcome this barrier., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
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- 2024
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38. Natural Product-Derived Compounds Targeting Keratinocytes and Molecular Pathways in Psoriasis Therapeutics.
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Lee YG, Jung Y, Choi HK, Lee JI, Lim TG, and Lee J
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- Humans, Animals, Receptors, Aryl Hydrocarbon metabolism, Molecular Targeted Therapy, Psoriasis drug therapy, Psoriasis metabolism, Keratinocytes drug effects, Keratinocytes metabolism, Biological Products pharmacology, Biological Products therapeutic use, Signal Transduction drug effects
- Abstract
Psoriasis is a chronic autoimmune inflammatory skin disorder that affects approximately 2-3% of the global population due to significant genetic predisposition. It is characterized by an uncontrolled growth and differentiation of keratinocytes, leading to the formation of scaly erythematous plaques. Psoriasis extends beyond dermatological manifestations to impact joints and nails and is often associated with systemic disorders. Although traditional treatments provide relief, their use is limited by potential side effects and the chronic nature of the disease. This review aims to discuss the therapeutic potential of keratinocyte-targeting natural products in psoriasis and highlight their efficacy and safety in comparison with conventional treatments. This review comprehensively examines psoriasis pathogenesis within keratinocytes and the various related signaling pathways (such as JAK-STAT and NF-κB) and cytokines. It presents molecular targets such as high-mobility group box-1 (HMGB1), dual-specificity phosphatase-1 (DUSP1), and the aryl hydrocarbon receptor (AhR) for treating psoriasis. It evaluates the ability of natural compounds such as luteolin, piperine, and glycyrrhizin to modulate psoriasis-related pathways. Finally, it offers insights into alternative and sustainable treatment options with fewer side effects.
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- 2024
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39. Elaeocarpus sylvestris var. ellipticus Extract and Its Major Component, Geraniin, Inhibit Herpes Simplex Virus-1 Replication.
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Lee YG, Park DW, Kwon JE, Kim H, and Kang SC
- Abstract
Elaeocarpus sylvestris var. ellipticus (ES), which our research group had confirmed inhibits influenza A and SARS-CoV-2 viruses, was investigated to identify new potent and selective inhibitors of herpes simplex virus-1 (HSV-1) replication. To clarify the optimal condition for ES extract (ESE), ES was extracted at different concentrations of 0, 30, 50, 70, and 100%, to screen for its anti-HSV-1 effect. Among these ESE samples, ESE50 (50% concentration) exhibited the strongest inhibition of HSV-1 replication (EC
50 23.2 μg/mL) while showing low cytotoxicity on host cells (IC50 342.8 μg/mL). The treatment of ESE50 clearly demonstrated a decrease in the expression of ICP0 in the lungs of HSV-1-infected BALB/c nude mice, compared to the MOCK group. Geraniin, which was isolated from ESE50 and analyzed using ESI-MS and 1D-(1 H- and13 C-) and 2D-NMR, showed greater potency in inhibiting HSV-1 replication, as determined by the plaque reduction assay (EC50 8.3 μg/mL) and luciferase inhibition (EC50 36.9 μg/mL). The results demonstrate that ESE50 and geraniin show great potential as candidates for new drug discovery in the treatment of HSV-1 and related diseases.- Published
- 2024
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40. Glycerol Triacetate-Based Flame Retardant High-Temperature Electrolyte for the Lithium-Ion Battery.
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Wu X, Liu T, Lee YG, and Whitacre JF
- Abstract
Rechargeable batteries that can operate at elevated temperatures (>70 °C) with high energy density are long-awaited for industrial applications including mining, grid stabilization, naval, aerospace, and medical devices. However, the safety, cycle life, energy density, and cost of the available high-temperature battery technologies remain an obstacle primarily owing to the limited electrolyte options available. We introduce a flame-retardant electrolyte that can enable stable battery cycling at 100 °C by incorporating triacetin into the electrolyte system. Triacetin has excellent chemical stability with lithium metal, and conventional cathode materials can effectively reduce parasitic reactions and promises a good battery performance at elevated temperatures. Our findings reveal that Li-metal half-cells can be made that have high energy density, high Coulombic efficiency, and good cycle life with triacetin-based electrolytes and three different cathode chemistries. Moreover, the nail penetration test in a commercial-scale pouch battery using this new electrolyte demonstrated suppressed heat generation when the cell was damaged and excellent safety when using the triacetin-based electrolyte.
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- 2024
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41. Anti-Melanogenic Effects of Cnidium monnieri Extract via p38 Signaling-Mediated Proteasomal Degradation of Tyrosinase.
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Choi SH, Kim H, Hwang-Bo J, Kim KM, Kwon JE, Lee SR, Hwang SH, Kang SC, and Lee YG
- Abstract
Cnidium monnieri fructus is widely used in traditional Oriental medicine for treating female genital disorders, male impotence, frigidity, and skin-related conditions in East Asia. However, the role of C. monnieri fructus extract (CMFE) in melanin synthesis is not well elucidated. This study aimed to investigate the anti-melanogenesis effect and mechanism of action of CMFE in α-MSH-stimulated B16F10 cells. Intracellular melanin content and tyrosinase activity were measured in α-MSH-stimulated B16F10 cells treated with various concentrations of CMFE (0.5-5 μg/mL). mRNA and protein levels of tyrosinase and MITF were evaluated using qRT-PCR and ting. CMFE's effect on the proteasomal degradation of tyrosinase was confirmed using a proteasomal degradation inhibitor, MG132. CMFE treatment activated p38, a protein associated with proteasomal degradation. Treatment with CMFE at up to 5 μg/mL showed no significant cytotoxicity. CMFE significantly reduced α-MSH-stimulated melanin production (43.29 ± 3.55% decrease, p < 0.05) and cellular tyrosinase activity (31.14 ± 3.15% decrease, p < 0.05). Although mRNA levels of MITF and tyrosinase increased, CMFE suppressed tyrosinase protein levels. The suppressive effect of CMFE on tyrosinase protein was blocked by MG132. CMFE inhibited melanogenesis by promoting the proteasome degradation of tyrosinase through p38 activation. These findings suggest that CMFE has the potential to be a natural whitening agent for inhibiting melanogenesis.
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- 2024
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42. Preoperative smoking and robot-assisted radical cystectomy outcomes & complications in multicenter KORARC database.
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Choi J, Lee J, Hwang YB, Jeong BC, Lee S, Ku JH, Nam JK, Kim W, Lee JY, Hong SH, Rha KH, Han WK, Ham WS, Kang SG, Kang SH, Oh JJ, Lee YG, Kwon TG, Kim TH, Jeon SH, Lee SH, Park SY, Yoon YE, and Lee YS
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Retrospective Studies, Databases, Factual, Treatment Outcome, Republic of Korea epidemiology, Preoperative Period, Cystectomy adverse effects, Cystectomy methods, Urinary Bladder Neoplasms surgery, Urinary Bladder Neoplasms mortality, Urinary Bladder Neoplasms pathology, Robotic Surgical Procedures adverse effects, Robotic Surgical Procedures methods, Smoking adverse effects, Postoperative Complications epidemiology, Postoperative Complications etiology
- Abstract
To investigate the influence of preoperative smoking history on the survival outcomes and complications in a cohort from a large multicenter database. Many patients who undergo radical cystectomy (RC) have a history of smoking; however, the direct association between preoperative smoking history and survival outcomes and complications in patients with muscle-invasive bladder cancer (MIBC) who undergo robot-assisted radical cystectomy (RARC) remains unexplored. We conducted a retrospective analysis using data from 749 patients in the Korean Robot-Assisted Radical Cystectomy Study Group (KORARC) database, with an average follow-up duration of 30.8 months. The cohort was divided into two groups: smokers (n = 351) and non-smokers (n = 398). Propensity score matching was employed to address differences in sample size and baseline demographics between the two groups (n = 274, each). Comparative analyses included assessments of oncological outcomes and complications. After matching, smoking did not significantly affect the overall complication rate (p = 0.121). Preoperative smoking did not significantly increase the occurrence of complications based on complication type (p = 0.322), nor did it increase the readmission rate (p = 0.076). There were no perioperative death in either group. Furthermore, preoperative smoking history showed no significant impact on overall survival (OS) [hazard ratio (HR) = 0.87, interquartile range (IQR): 0.54-1.42; p = 0.589] and recurrence-free survival (RFS) (HR = 1.12, IQR: 0.83-1.53; p = 0.458) following RARC for MIBC. The extent of preoperative smoking (≤ 10, 10-30, and ≥ 30 pack-years) had no significant influence on OS and RFS in any of the categories (all p > 0.05). Preoperative smoking history did not significantly affect OS, RFS, or complications in patients with MIBC undergoing RARC., (© 2024. The Author(s).)
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- 2024
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43. Evaluating the effect of a mobile-based symptom monitoring system for improving physical function in patients with cancer during chemotherapy: study protocol for a multicentre randomised controlled trial.
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Lee M, Kang D, Um Y, Jo B, Rhue J, Park S, Lee YY, Noh JJ, Lee YG, Koo DH, Park KH, Lee S, Ahn JS, Oh D, and Cho J
- Subjects
- Adult, Female, Humans, Male, Antineoplastic Agents therapeutic use, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Republic of Korea, Telemedicine, Mobile Applications, Neoplasms drug therapy, Quality of Life
- Abstract
Introduction: Symptoms due to chemotherapy are common in patients with cancer. Cancer-related symptoms are closely associated with the deterioration of physical function which can be associated with decreased quality of life and increased mortality. Thus, timely symptom identification is critical for improving cancer prognosis and survival. Recently, remote symptom monitoring system using digital technology has demonstrated its effects on symptom control or survival. However, few studies examined whether remote monitoring would contribute to retaining physical function among patients with cancer. Therefore, this study aimed to evaluate the effectiveness of mobile-based symptom monitoring in improving physical function among patients with cancer under chemotherapy., Methods and Analysis: This study is a multicentre, open-label, parallel-group, randomised controlled trial. We will recruit 372 patients at three tertiary hospitals located in Seoul, South Korea. Study participants will be randomly assigned to either an intervention group receiving the ePRO-CTCAE app and a control group receiving routine clinical practice only. The primary outcome is changes in physical function from commencement to completion of planned chemotherapy. A linear mixed model will be performed under the intention-to-treat principle. The secondary outcomes include physical activity level; changes in pain interference; changes in depressive symptom; unplanned clinical visits; additional medical expenditure for symptom management; completion rate of planned chemotherapy; changes in symptom burden and health-related quality of life; and 1-year overall mortality., Ethics and Dissemination: The study has been approved by the institutional review board and ethics committee at the three university hospitals involved in this trial. Written informed consent will be obtained from all the participants. The results of the trial will be submitted for publication in peer-reviewed academic journals and disseminated through relevant literatures., Trial Registration Number: KCT0007220., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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44. Actinidia arguta Extract Containing Myo -Inositol Suppresses TNF- α -Induced VCAM-1 Expression and Monocyte Adhesion to Endothelial Cells via Inhibition of the PTEN/Akt/GSK-3 β and NF- κ B Signaling Pathways.
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Lee J, Park J, Song KM, Lee YG, and Choi HK
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- Humans, Animals, Mice, Mice, Inbred C57BL, Atherosclerosis metabolism, Atherosclerosis drug therapy, Male, Vascular Cell Adhesion Molecule-1 metabolism, Vascular Cell Adhesion Molecule-1 genetics, NF-kappa B metabolism, NF-kappa B genetics, Monocytes drug effects, Monocytes metabolism, Proto-Oncogene Proteins c-akt metabolism, Proto-Oncogene Proteins c-akt genetics, PTEN Phosphohydrolase metabolism, PTEN Phosphohydrolase genetics, Tumor Necrosis Factor-alpha metabolism, Tumor Necrosis Factor-alpha genetics, Actinidia chemistry, Plant Extracts pharmacology, Signal Transduction drug effects, Human Umbilical Vein Endothelial Cells drug effects, Glycogen Synthase Kinase 3 beta metabolism, Glycogen Synthase Kinase 3 beta genetics, Cell Adhesion drug effects, Inositol pharmacology, Inositol analogs & derivatives
- Abstract
The primary inflammatory process in atherosclerosis, a major contributor to cardiovascular disease, begins with monocyte adhering to vascular endothelial cells. Actinidia arguta (kiwiberry) is an edible fruit that contains various bioactive components. While A. arguta extract (AAE) has been recognized for its anti-inflammatory characteristics, its specific inhibitory effect on early atherogenic events has not been clarified. We used tumor necrosis factor- α (TNF- α )-stimulated human umbilical vein endothelial cells (HUVECs) for an in vitro model. AAE effectively hindered the attachment of THP-1 monocytes and reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) in HUVECs. Transcriptome analysis revealed that AAE treatment upregulated phosphatase and tensin homolog (PTEN), subsequently inhibiting phosphorylation of AKT and glycogen synthase kinase 3 β (GSK3 β ) in HUVECs. AAE further hindered phosphorylation of AKT downstream of the nuclear factor kappa B (NF- κ B) signaling pathway, leading to suppression of target gene expression. Oral administration of AAE suppressed TNF- α -stimulated VCAM-1 expression, monocyte-derived macrophage infiltration, and proinflammatory cytokine expression in C57BL/6 mouse aortas. Myo -inositol, identified as the major compound in AAE, played a key role in suppressing THP-1 monocyte adhesion in HUVECs. These findings suggest that AAE could serve as a nutraceutical for preventing atherosclerosis by inhibiting its initial pathogenesis.
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- 2024
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45. Self-Buffering system for Cost-Effective production of lactic acid from glucose and xylose using Acid-Tolerant Issatchenkia orientalis.
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Lee YG, Kang NK, Kim C, Tran VG, Cao M, Yoshikuni Y, Zhao H, and Jin YS
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- Glucose, Cost-Benefit Analysis, Fermentation, Saccharomyces cerevisiae, Lactic Acid, Xylose, Pichia
- Abstract
This study presents a cost-effective strategy for producing organic acids from glucose and xylose using the acid-tolerant yeast, Issatchenkia orientalis. I. orientalis was engineered to produce lactic acid from xylose, and the resulting strain, SD108XL, successfully converted sorghum hydrolysates into lactic acid. In order to enable low-pH fermentation, a self-buffering strategy, where the lactic acid generated by the SD108XL strain during fermentation served as a buffer, was developed. As a result, the SD108 strain produced 67 g/L of lactic acid from 73 g/L of glucose and 40 g/L of xylose, simulating a sugar composition of sorghum biomass hydrolysates. Moreover, techno-economic analysis underscored the efficiency of the self-buffering strategy in streamlining the downstream process, thereby reducing production costs. These results demonstrate the potential of I. orientalis as a platform strain for the cost-effective production of organic acids from cellulosic hydrolysates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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46. Polymerized Human Hemoglobin-Based Oxygen Carrier Preserves Lung Allograft Function During Normothermic Ex Vivo Lung Perfusion.
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Cuddington C, Greenfield A, Lee YG, Kim JL, Lamb D, Buehler PW, Black SM, Palmer AF, and Whitson BA
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- Animals, Rats, Humans, Male, Lung, Oxygen metabolism, Allografts, Hemolysis drug effects, Erythrocytes, Hemoglobins administration & dosage, Lung Transplantation methods, Lung Transplantation adverse effects, Perfusion methods, Blood Substitutes pharmacology, Rats, Sprague-Dawley
- Abstract
Normothermic ex vivo lung perfusion (EVLP) can resuscitate marginal lung allografts to increase organs available for transplantation. During normothermic perfusion, cellular metabolism is more active compared with subnormothermic perfusion, creating a need for an oxygen (O 2 ) carrier in the perfusate. As an O 2 carrier, red blood cells (RBCs) are a scarce resource and are susceptible to hemolysis in perfusion circuits, thus releasing cell-free hemoglobin (Hb), which can extravasate into the tissue space, thus promoting scavenging of nitric oxide (NO) and oxidative tissue damage. Fortunately, polymerized human Hb (PolyhHb) represents a synthetic O 2 carrier with a larger molecular diameter compared with Hb, preventing extravasation, and limiting adverse reactions. In this study, a next-generation PolyhHb-based perfusate was compared to both RBC and asanguinous perfusates in a rat EVLP model. During EVLP, the pulmonary arterial pressure and pulmonary vascular resistance were both significantly higher in lungs perfused with RBCs, which is consistent with RBC hemolysis. Lungs perfused with PolyhHb demonstrated greater oxygenation than those perfused with RBCs. Post-EVLP analysis revealed that the PolyhHb perfusate elicited less cellular damage, extravasation, iron tissue deposition, and edema than either RBCs or colloid control. These results show promise for a next-generation PolyhHb to maintain lung function throughout EVLP., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)
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- 2024
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47. Applications of artificial intelligence in urologic oncology.
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Pak S, Park SG, Park J, Cho ST, Lee YG, and Ahn H
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- Humans, Prostatic Neoplasms therapy, Kidney Neoplasms, Urinary Bladder Neoplasms therapy, Male, Medical Oncology methods, Deep Learning, Machine Learning, Artificial Intelligence, Urologic Neoplasms therapy
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Purpose: With the recent rising interest in artificial intelligence (AI) in medicine, many studies have explored the potential and usefulness of AI in urological diseases. This study aimed to comprehensively review recent applications of AI in urologic oncology., Materials and Methods: We searched the PubMed-MEDLINE databases for articles in English on machine learning (ML) and deep learning (DL) models related to general surgery and prostate, bladder, and kidney cancer. The search terms were a combination of keywords, including both "urology" and "artificial intelligence" with one of the following: "machine learning," "deep learning," "neural network," "renal cell carcinoma," "kidney cancer," "urothelial carcinoma," "bladder cancer," "prostate cancer," and "robotic surgery.", Results: A total of 58 articles were included. The studies on prostate cancer were related to grade prediction, improved diagnosis, and predicting outcomes and recurrence. The studies on bladder cancer mainly used radiomics to identify aggressive tumors and predict treatment outcomes, recurrence, and survival rates. Most studies on the application of ML and DL in kidney cancer were focused on the differentiation of benign and malignant tumors as well as prediction of their grade and subtype. Most studies suggested that methods using AI may be better than or similar to existing traditional methods., Conclusions: AI technology is actively being investigated in the field of urological cancers as a tool for diagnosis, prediction of prognosis, and decision-making and is expected to be applied in additional clinical areas soon. Despite technological, legal, and ethical concerns, AI will change the landscape of urological cancer management., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)
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- 2024
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48. Streamlined measurement of chimeric antigen receptor T-cell concentration, size, viability and two-color phenotyping during manufacturing.
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Pajarillo R, Paruzzo L, Carturan A, Ugwuanyi O, White G, Guruprasad P, Ballard HJ, Patel RP, Zhang Y, Lee YG, Hong SJA, Dittami GM, and Ruella M
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- Humans, Antigens, CD19 immunology, Antigens, CD19 metabolism, Phenotype, Receptors, Antigen, T-Cell immunology, Receptors, Antigen, T-Cell metabolism, Immunophenotyping methods, Cell Size, Receptors, Chimeric Antigen immunology, Receptors, Chimeric Antigen metabolism, Cell Survival, Flow Cytometry methods, Immunotherapy, Adoptive methods, T-Lymphocytes immunology, T-Lymphocytes metabolism
- Abstract
Background Aims: The successful development of CD19-targeted chimeric antigen receptor (CAR) T-cell therapies has led to an exponential increase in the number of patients recieving treatment and the advancement of novel CAR T products. Therefore, there is a strong need to develop streamlined platforms that allow rapid, cost-effective, and accurate measurement of the key characteristics of CAR T cells during manufacturing (i.e., cell number, cell size, viability, and basic phenotype)., Methods: In this study, we compared the novel benchtop cell analyzer Moxi GO II (ORFLO Technologies), which enables simultaneous evaluation of all the aforementioned parameters, with current gold standards in the field: the Multisizer Coulter Counter (cell counter) and the BD LSRFortessa (flow cytometer)., Results: Our results demonstrated that the Moxi GO II can accurately measure cell number and cell size (i.e., cell volume) while simultaneously assessing simple two-color flow cytometry parameters, such as CAR T-cell viability and CD4 or CAR expression., Conclusions: These measurements are comparable with those of gold standard instruments, demonstrating that the Moxi GO II is a promising platform for quickly monitoring CAR T-cell growth and phenotype in research-grade and clinical samples., Competing Interests: Declaration of Competing Interest MR holds patents related to CAR T cells that are licensed to Novartis, Tmunity (Kite) and viTToria biotherapeutics. MR has served as a consultant for nanoString, BMS, GSK, GLG, GuidePoint, Sana, Bayer and AbClon. MR receives research funding from AbClon, Beckman Coulter, Oxford Nano Imaging, Curiox and viTToria biotherapeutics. MR is the scientific founder of viTToria biotherapeutics. The Ruella laboratory was provided a Moxi GO II device and supplies to perform this study. GD is an employee of ORFLO Technologies. All other authors declare no competing interests., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2024
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49. Alteration of medial temporal lobe metabolism related to Alzheimer's disease and dementia with lewy bodies.
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Kang S, Jeon S, Lee YG, and Ye BS
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- Humans, Female, Male, Aged, Aged, 80 and over, Middle Aged, Lewy Body Disease metabolism, Lewy Body Disease diagnostic imaging, Alzheimer Disease metabolism, Alzheimer Disease diagnostic imaging, Positron-Emission Tomography, Temporal Lobe metabolism, Temporal Lobe diagnostic imaging, Fluorodeoxyglucose F18, Neuropsychological Tests
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Background: Association of medial temporal lobe (MTL) metabolism with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) has not been evaluated considering their mixed disease (MD)., Methods: 131 patients with AD, 133 with DLB, 122 with MD, and 28 normal controls (NCs) underwent neuropsychological tests, assessments for parkinsonism, cognitive fluctuation (CF), and visual hallucinations (VH), and
18 F-fluorodeoxyglucose PET to quantify MTL metabolism in the amygdala, hippocampus, and entorhinal cortex. The effects of AD and DLB on MTL metabolism were evaluated using general linear models (GLMs). Associations between MTL metabolism, cognition, and clinical features were evaluated using GLMs or logistic regression models separately performed for the AD spectrum (NC + AD + MD), DLB spectrum (NC + DLB + MD), and disease groups (AD + DLB + MD). Covariates included age, sex, and education., Results: AD was associated with hippocampal/entorhinal hypometabolism, whereas DLB was associated with relative amygdalar/hippocampal hypermetabolism. Relative MTL hypermetabolism was associated with lower attention/visuospatial/executive scores and severe parkinsonism in both the AD and DLB spectra and disease groups. Left hippocampal/entorhinal hypometabolism was associated with lower verbal memory scores, whereas right hippocampal hypometabolism was associated with lower visual memory scores in both the AD spectrum and disease groups. Relative MTL hypermetabolism was associated with an increased risk of CF and VH in the disease group, and relative amygdalar hypermetabolism was associated with an increased risk of VH in the DLB spectrum., Conclusions: Entorhinal-hippocampal hypometabolism and relative amygdala-hippocampal hypermetabolism could be characteristics of AD- and DLB-related neurodegeneration, respectively., (© 2024. The Author(s).)- Published
- 2024
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50. Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR - or ALK -Mutated Non-Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04).
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Park S, Kim TM, Han JY, Lee GW, Shim BY, Lee YG, Kim SW, Kim IH, Lee S, Kim YJ, Park JH, Park SG, Lee KH, Kang EJ, Kim JW, Shin SH, Ock CY, Nam BH, Lee J, Jung HA, Sun JM, Lee SH, Ahn JS, and Ahn MJ
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- Humans, Bevacizumab, Carboplatin, B7-H1 Antigen therapeutic use, Pemetrexed therapeutic use, ErbB Receptors genetics, Receptor Protein-Tyrosine Kinases therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Antibodies, Monoclonal, Humanized
- Abstract
Purpose: In the treatment of non-small-cell lung cancer (NSCLC) with a driver mutation, the role of anti-PD-(L)1 antibody after tyrosine kinase inhibitor (TKI) remains unclear. This randomized, open-label, multicenter, phase III study evaluates the efficacy of atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP ) in EGFR- or ALK -mutated NSCLC that progressed before TKI therapy., Materials and Methods: We compared the clinical efficacy of ABCP followed by maintenance therapy with atezolizumab plus bevacizumab with pemetrexed plus carboplatin or cisplatin (PC) followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS)., Results: A total of 228 patients with activating EGFR mutation (n = 215) or ALK translocation (n = 13) were enrolled from 16 sites in the Republic of Korea and randomly assigned at 2:1 ratio to either ABCP (n = 154) or PC arm (n = 74). The median follow-up duration was 26.1 months (95% CI, 24.7 to 28.2). Objective response rates (69.5% v 41.9%, P < .001) and median PFS (8.48 v 5.62 months, hazard ratio [HR], 0.62 [95% CI, 0.45 to 0.86]; P = .004) were significantly better in the ABCP than PC arm. PFS benefit increased as PD-L1 expression increased, with an HR of 0.47, 0.41, and 0.24 for PD-L1 ≥1%, ≥10%, and ≥50%, respectively. Overall survival was similar between ABCP and PC arm (20.63 v 20.27 months, HR, 1.01 [95% CI, 0.69 to 1.46]; P = .975). The safety profile of the ABCP arm was comparable with that previously reported, with no additional safety signals, but higher rates of treatment-related adverse events were observed compared with the PC arm., Conclusion: To our knowledge, this study is the first randomized phase III study to demonstrate the clinical benefit of anti-PD-L1 antibody in combination with bevacizumab and chemotherapy in patients with EGFR- or ALK -mutated NSCLC who have progressed on relevant targeted therapy.
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- 2024
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