المؤلفون: Joo Hee Jeong, Hyoung Seok Lee, Yun Young Choi, Yun Gi Kim, Jaemin Shim, Jin Ha Hwang, Seung Gyu Yun, Yun Jung Cho, Young-Hoon Kim, Jong-Il Choi

المصدر: International Journal of Arrhythmia, Vol 25, Iss 1, Pp 1-11 (2024)

مصطلحات موضوعية: Brugada syndrome, Arrhythmogenic cardiomyopathy, High-throughput nucleotide sequencing, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Abstract Background Brugada syndrome (BrS) and arrhythmogenic cardiomyopathy (ACM) are inherited cardiac diseases that may predispose to ventricular arrhythmia. Although overlapping features between BrS and ACM have been demonstrated previously, it remains to be determined whether genetic testing for ACM-related genes is needed in BrS probands. Method Based on a single-center, retrospective registry of BrS, we aimed to verify genetic profiles of BrS using a next-generation sequencing panel, and further analyzed genetic testing of ACM-related variants in Brugada phenotypes. Results Among a total of 119 Brugada phenotypes, 114 patients (95.8%) were male and the mean age of onset was 43.6 years. Genetic variants were identified in 25 of the 42 patients who underwent genetic testing. Fifteen patients had BrS-related genotypes, including SCN5A in 6 patients, and non-SCN5A genes in 9 patients (SCN10A, HCN4, SCN3B, and KCNE3). Nineteen patients underwent additional genetic testing with cardiomyopathy panel, which revealed ACM-related genotypes (2 PKP2, 1 DSG2, 1 TMEM43, 1 JUP, and 1 DSP) present in 6 patients (31.5%). None of the patients had structural or electrocardiographic features that fulfilled the diagnostic criteria for ACM. Conclusions In clinical setting, ACM-related genes were identified in a significant proportion of Brugada phenotypes, supporting the argument that genetic testing of ACM overlapping is needed. Follow-up imaging studies should be considered to monitor if the disease progresses to ACM.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2466-1171Test

الوصول الحر: https://doaj.org/article/2f9176e0aa6f4933915e75fa69399776Test

المؤلفون: Dongheon Lee, Ja Gyung Kim, Tae Wan Kim, Jong-il Choi

المصدر: AMB Express, Vol 14, Iss 1, Pp 1-7 (2024)

مصطلحات موضوعية: Non-canonical amino acid, Methanosaeta concilii, Aminoacyl-tRNA synthetase, Para-azido-L-phenylalanine, Amber suppression, Biotechnology, TP248.13-248.65, Microbiology, QR1-502

الوصف: Abstract Genetic code expansion involves introducing non-canonical amino acids (ncAAs) with unique functional groups into proteins to broaden their applications. Orthogonal aminoacyl tRNA synthetase (aaRS), essential for genetic code expansion, facilitates the charging of ncAAs to tRNA. In this study, we developed a new aaRS mutant from Methanosaeta concilii tyrosyl-tRNA synthetase (Mc TyrRS) to incorporate para-azido-l-phenylalanine (AzF). The development involved initial site-specific mutations in Mc TyrRS, followed by random mutagenesis. The new aaRS mutant with amber suppression was isolated through fluorescence-activated cell sorting. The M. concilii aaRS mutant structure was further analyzed to interpret the effect of mutations. This research provides a novel orthogonal aaRS evolution pipeline for highly efficient ncAA incorporation that will contribute to developing novel aaRS from various organisms.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2191-0855Test

الوصول الحر: https://doaj.org/article/d7c7c6a369c54650baaa05f04d7c76beTest

المؤلفون: Eun Byeol Go, Jae Hun Lee, Jeong Haeng Cho, Na Hyun Kwon, Jong-il Choi, Inchan Kwon

المصدر: Journal of Biological Engineering, Vol 18, Iss 1, Pp 1-12 (2024)

مصطلحات موضوعية: Single-chain variable fragment, Therapeutic antibody, Human serum albumin, Site-specific conjugation, Half-life extension, Biology (General), QH301-705.5

الوصف: Abstract Background The use of single-chain variable fragments (scFvs) for treating human diseases, such as cancer and immune system disorders, has attracted significant attention. However, a critical drawback of scFv is its extremely short serum half-life, which limits its therapeutic potential. Thus, there is a critical need to prolong the serum half-life of the scFv for clinical applications. One promising serum half-life extender for therapeutic proteins is human serum albumin (HSA), which is the most abundant protein in human serum, known to have an exceptionally long serum half-life. However, conjugating a macromolecular half-life extender to a small protein, such as scFv, often results in a significant loss of its critical properties. Results In this study, we conjugated the HSA to a permissive site of scFv to improve pharmacokinetic profiles. To ensure minimal damage to the antigen-binding capacity of scFv upon HSA conjugation, we employed a site-specific conjugation approach using a heterobifunctional crosslinker that facilitates thiol-maleimide reaction and inverse electron-demand Diels-Alder reaction (IEDDA). As a model protein, we selected 4D5scFv, derived from trastuzumab, a therapeutic antibody used in human epithermal growth factor 2 (HER2)-positive breast cancer treatment. We introduced a phenylalanine analog containing a very reactive tetrazine group (frTet) at conjugation site candidates predicted by computational methods. Using the linker TCO-PEG4-MAL, a single HSA molecule was site-specifically conjugated to the 4D5scFv (4D5scFv-HSA). The 4D5scFv-HSA conjugate exhibited HER2 binding affinity comparable to that of unmodified 4D5scFv. Furthermore, in pharmacokinetic profile in mice, the serum half-life of 4D5scFv-HSA was approximately 12 h, which is 85 times longer than that of 4D5scFv. Conclusions The antigen binding results and pharmacokinetic profile of 4D5scFv-HSA demonstrate that the site-specifically albumin-conjugated scFv retained its binding affinity with a prolonged serum half-life. In conclusion, we developed an effective strategy to prepare site-specifically albumin-conjugated 4D5scFv, which can have versatile clinical applications with improved efficacy.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1754-1611Test

الوصول الحر: https://doaj.org/article/f6190c0324714d5ab25c6d715ffe904dTest

المؤلفون: Yun Gi Kim, Dong Yun Kim, Seung-Young Roh, Joo Hee Jeong, Hyoung Seok Lee, Kyongjin Min, Yun Young Choi, Kyung-Do Han, Jaemin Shim, Jong-Il Choi, Young-Hoon Kim

المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-10 (2024)

مصطلحات موضوعية: Sudden cardiac arrest, Atrial fibrillation, Ventricular arrhythmia, Alcohol, Medicine, Science

الوصف: Abstract The risk of having atrial fibrillation (AF) is associated with alcohol intake. However, it is not clear whether sudden cardiac arrest (SCA) and ventricular arrhythmia (VA) including ventricular tachycardia, flutter, or fibrillation have similar associations with alcohol. We aimed to evaluate the association of alcohol intake with all-cause death, new-onset AF, VA, and SCA using single cohort with a sufficient sample size. A total of 3,990,373 people without a prior history of AF, VAs, or SCA was enrolled in this study based on nationwide health check-up in 2009. We classified the participants into four groups according to weekly alcohol consumption, and evaluated the association of alcohol consumption with each outcome. We observed a significant association between mild (hazard ratio [HR] = 0.826; 95% confidence interval [CI] = 0.815–0.838) to moderate (HR = 0.930; 95% CI = 0.912–0.947) drinking with decreased risk of all-cause mortality. However heavy drinking (HR = 1.108; 95% CI = 1.087–1.129) was associated with increased all-cause death. The risk of new-onset AF was significantly associated with moderate (HR = 1.129; 95% CI = 1.097–1.161) and heavy (HR = 1.298; 95% CI = 1.261–1.337) drinking. However, the risk of SCA showed negative association with all degrees of alcohol intake: 20% (HR = 0.803; 95% CI = 0.769–0.839), 15% (HR = 0.853; 95% CI = 0.806–0.902), and 8% (HR = 0.918; 95% CI = 0.866–0.974) lower risk for mild, moderate, and heavy drinkers, respectively. Mild drinking was associated with reduced risk of VA with moderate and heavy drinking having no associations. In conclusion, the association between alcohol and various outcomes in this study were heterogeneous. Alcohol might have different influences on various cardiac disorders.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/6d5f7601db0c498ebdb916aeb2ac1ad0Test

المؤلفون: Wataru Shimizu, Fred M. Kusumoto, Michael‐Joseph F. Agbayani, Sirin Apiyasawat, Minglong Chen, Chi Keong Ching, Jong‐Il Choi, Van Buu Dan Do, Dicky A. Hanafy, Jodie L. Hurwitz, Sofian Johar, Jonathan M. Kalman, Aamir Hameed H. Khan, Pichmanil Khmao, Andrew D. Krahn, Tachapong Ngarmukos, Son Thai Binh Nguyen, Nwe Nwe, Seil Oh, Kyoko Soejima, Martin K. Stiles, Hsuan‐Ming Tsao, Saruul Tseveendee

المصدر: Journal of Arrhythmia, Vol 40, Iss 1, Pp 1-16 (2024)

مصطلحات موضوعية: arrhythmia, Asia, electrophysiology, global, Pacific, summit, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Abstract On May 27, 2022, the Asia Pacific Heart Rhythm Society and the Heart Rhythm Society convened a meeting of leaders from different professional societies of healthcare providers committed to arrhythmia care from the Asia Pacific region. The overriding goals of the meeting were to discuss clinical and health policy issues that face each country for providing care for patients with electrophysiologic issues, share experiences and best practices, and discuss potential future solutions. Participants were asked to address a series of questions in preparation for the meeting. The format of the meeting was a series of individual country reports presented by the leaders from each of the professional societies followed by open discussion. The recorded presentations from the Asia Summit can be accessed at https://www.heartrhythm365.org/URL/asiasummitTest‐22. Three major themes arose from the discussion. First, the major clinical problems faced by different countries vary. Although atrial fibrillation is common throughout the region, the most important issues also include more general issues such as hypertension, rheumatic heart disease, tobacco abuse, and management of potentially life‐threatening problems such as sudden cardiac arrest or profound bradycardia. Second, there is significant variability in the access to advanced arrhythmia care throughout the region because of differences in workforce availability, resources, drug availability, and national health policies. Third, collaboration in the area already occurs between individual countries, but no systematic regional method for working together is present.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1880-4276Test; https://doaj.org/toc/1883-2148Test

الوصول الحر: https://doaj.org/article/8aa83d461c254f5e87cb0bbff0637019Test

المؤلفون: JungMin Choi, So-Ryoung Lee, Soonil Kwon, Hyo-Jeong Ahn, Kyung-Yeon Lee, Jong-Sung Park, Jong-Il Choi, Sung Ho Lee, Jung Ho Heo, Il-Young Oh, Young Keun On, Hee Tae Yu, Kwang-No Lee, Nam-Ho Kim, Hyung Wook Park, Ki Hong Lee, Seung Yong Shin, Seil Oh, Gregory Y. H. Lip, Seongwook Han, Eue-Keun Choi

المصدر: Frontiers in Cardiovascular Medicine, Vol 11 (2024)

مصطلحات موضوعية: apixaban, atrial fibrillation, dose, clinical characteristics, off-label reduced dose, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: BackgroundData on off-label reduced dose risk among patients with atrial fibrillation (AF) who qualify for a single-dose reduction of apixaban is scarce.ObjectivesWe prospectively assessed apixaban dosing and clinical characteristics in AF patients meeting a dose reduction criterion.MethodsThe multicentre, prospective cohort study, the efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE), encompasses patients with AF who met the criteria for a single-dose reduction of apixaban and were given varying doses of apixaban, either the on-label standard dose or the off-label reduced dose.ResultsOf 2,000 patients (mean age 74.3 ± 7.9 years, 55.8% women), 29.7% were ≥80 years, 62.6% weighed ≤60 kg, and 7.8% had serum creatinine ≥1.5 mg/dL. Of these, 51.3% were prescribed an off-label reduced dose of apixaban. The off-label group was characterized with older age, more comorbidities, and antiplatelet agents, while the on-label group had more prior strokes. Physicians preferred off-label reduced dose in the “marginal zone,” defined as age 75–80 years, weight 60–65 kg, and creatinine levels 1.2–1.5 mg/dL.ConclusionsIn real-world clinical setting of the Korean population, off-label reduced dose apixaban was administered to nearly half of the patients who qualified for a single dose reduction. This reduced dosage was more commonly prescribed to patients with frail characteristics, while patients with a history of stroke were more often given the standard dose as per the label. A future study is planned to contrast the safety and effectiveness of the standard dose against the reduced dose of apixaban in this population.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fcvm.2024.1367623/fullTest; https://doaj.org/toc/2297-055XTest

الوصول الحر: https://doaj.org/article/50e48bf245da4ef2baeee376c1daa815Test

المؤلفون: Yun Gi Kim, Kyongjin Min, Joo Hee Jeong, Seung-Young Roh, Kyung-Do Han, Jaemin Shim, Jong-Il Choi, Young-Hoon Kim

المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-11 (2024)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract Hypertension is a known risk factor for sudden cardiac arrest (SCA). However, the role of temporal changes in blood pressure on the risk of SCA is not fully understood. This study was conducted to determine whether a temporal increase or decrease in blood pressure is associated with the risk of SCA. This study was based on nationwide healthcare insurance data. Individuals who underwent nationwide health check-ups in 2009 and 2011 were analyzed. A total of 2,801,153 individuals were evaluated for 8100 SCA events during the 17, 740, 420 person-years of follow-up. In a multivariate analysis, there were linear association between the degree of temporal elevation of systolic blood pressure (SBP) and the risk of SCA: (i) adjusted-hazard ratio (HR) 1.11 (p = 0.001) in 10 ≤ ΔSBP

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/9f3601326ac144f982d30fee1a995b17Test

المؤلفون: Joo Hee Jeong, Yun Gi Kim, Kyung-Do Han, Seung-Young Roh, Hyoung Seok Lee, Yun Young Choi, Jaemin Shim, Jong-Il Choi, Young-Hoon Kim

المصدر: Cardiovascular Diabetology, Vol 23, Iss 1, Pp 1-10 (2024)

مصطلحات موضوعية: Underweight, Diabetes mellitus, Sudden cardiac arrest, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Abstract Background Underweight imposes significant burden on cardiovascular outcomes in patients with diabetes mellitus. However, less is known about the impact of serial change in body weight status measured as body mass index (BMI) on the risk of sudden cardiac arrest (SCA). This study investigated the association between SCA and temporal change in BMI among patients with diabetes mellitus. Methods Based on Korean National Health Insurance Service database, participants with diabetes mellitus who underwent health examination between 2009 and 2012 and had prior health examination data (four years ago, 2005–2008) were retrospectively analyzed. BMI was measured at baseline (2005–2008) and 4-year follow-up health examination (2009–2012). Patients were classified in four groups according to the body weight status and its temporal change: sustained non-underweight, sustained underweight, previous underweight, and newly developed underweight. Primary outcome was defined as occurrence of SCA. Results A total of 1,355,746 patients with diabetes mellitus were included for analysis, and SCA occurred in 12,554 cases. SCA was most common in newly developed underweight (incidence rate = 4.45 per 1,000 person-years), followed by sustained underweight (incidence rate = 3.90), previous underweight (incidence rate = 3.03), and sustained non-underweight (incidence rate = 1.34). Adjustment of covariates resulted highest risk of SCA in sustained underweight (adjusted hazard ratio = 2.60, 95% confidence interval [2.25–3.00], sustained non-underweight as a reference), followed by newly developed underweight (2.42, [2.15–2.74]), and previous underweight (2.12, [1.77–2.53]). Conclusions In diabetes mellitus, sustained underweight as well as decrease in body weight during 4-year follow-up imposes substantial risk on SCA. Recovery from underweight over time had relatively lower, but yet increased risk of SCA. Both underweight and dynamic decrease in BMI can be associated with increased risk of SCA.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1475-2840Test

الوصول الحر: https://doaj.org/article/fac98d1d798d4656868ef7a9e3ade87cTest

المؤلفون: Jeonghaeng Cho, Byungseop Yang, Jae Hun Lee, Hyunwoo Kim, Hyeongseok Kim, Eun Byeol Go, Dong-ho Bak, Su Jin Park, Inchan Kwon, Jong-il Choi, Kyunghee Lee

المصدر: Arthritis Research & Therapy, Vol 25, Iss 1, Pp 1-11 (2023)

مصطلحات موضوعية: Gout, Urate oxidase, AfUox, rHA, Site-specific conjugation, IEDDA, Diseases of the musculoskeletal system, RC925-935

الوصف: Abstract Background Exogenously providing engineered Uox with enhanced half-life is one of the important urate-lowering treatments for gout. The potential of PAT101, a recombinant human albumin (rHA)-conjugated variant, was evaluated and compared as a novel gout treatment through various in vivo studies with PAT101 and competing drugs. Methods PAT101 was produced by site-specific conjugation of rHA and Aspergillus flavus Uox (AfUox-rHA) through clickable non-natural amino acid (frTet) and Inverse electron demand Diels–Alder (IEDDA) reaction. In vivo pharmacokinetics, efficacy tests and in vitro immunogenetic assay were performed after single or multiple doses of PAT101 and its competitors in BALB/c mice, transgenic (TG) mice, Sprague–Dawley (SD) rats, and non-human primate (NHP). Results The half-life of PAT101 in single-dose treated TG mice was more than doubled compared to pegloticase. In SD rats with 4 weeks of repeated administration of rasburicase, only 24% of Uox activity remained, whereas in PAT101, it was maintained by 86%. In the Uox KO model, the survival rate of PAT101 was comparable to that of pegloticase. In addition, human PBMC-based CD4+/CD8+ T-cell activation analysis demonstrated that PAT101 has a lower immune response compared to the original drug, rasburicase. Conclusion All results suggest that this rHA-conjugated AfUox, PAT101, can be provided as a reliable source of Uox for gout treatment.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1478-6362Test

الوصول الحر: https://doaj.org/article/ac493dc4a51e4b37abab1ac829f0460fTest

المؤلفون: Jong-Il Choi, Songsak Kiatchoosakun, Panyapat Jiampo, Hung Fat Tse, Yannie Oi Yan Soo, Chun-Chieh Wang, Chang Hoon Lee, Ladislav Pecen, Martin Unverdorben, Raffaele De Caterina, Paulus Kirchhof

المصدر: Circulation Reports. 2024, 6(3):86-93