1.Construction and validation of a synthetic phage-displayed nanobody library
Minju KIM ; Xuelian BAI ; Hyewon IM ; Jisoo YANG ; Youngju KIM ; Minjoo MJ KIM ; Yeonji OH ; Yuna JEON ; Hayoung KWON ; Seunghyun LEE ; Chang-Han LEE
The Korean Journal of Physiology and Pharmacology 2024;28(5):457-467
Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.
2.Construction and validation of a synthetic phage-displayed nanobody library
Minju KIM ; Xuelian BAI ; Hyewon IM ; Jisoo YANG ; Youngju KIM ; Minjoo MJ KIM ; Yeonji OH ; Yuna JEON ; Hayoung KWON ; Seunghyun LEE ; Chang-Han LEE
The Korean Journal of Physiology and Pharmacology 2024;28(5):457-467
Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.
3.Construction and validation of a synthetic phage-displayed nanobody library
Minju KIM ; Xuelian BAI ; Hyewon IM ; Jisoo YANG ; Youngju KIM ; Minjoo MJ KIM ; Yeonji OH ; Yuna JEON ; Hayoung KWON ; Seunghyun LEE ; Chang-Han LEE
The Korean Journal of Physiology and Pharmacology 2024;28(5):457-467
Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.
4.Construction and validation of a synthetic phage-displayed nanobody library
Minju KIM ; Xuelian BAI ; Hyewon IM ; Jisoo YANG ; Youngju KIM ; Minjoo MJ KIM ; Yeonji OH ; Yuna JEON ; Hayoung KWON ; Seunghyun LEE ; Chang-Han LEE
The Korean Journal of Physiology and Pharmacology 2024;28(5):457-467
Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.
5.Construction and validation of a synthetic phage-displayed nanobody library
Minju KIM ; Xuelian BAI ; Hyewon IM ; Jisoo YANG ; Youngju KIM ; Minjoo MJ KIM ; Yeonji OH ; Yuna JEON ; Hayoung KWON ; Seunghyun LEE ; Chang-Han LEE
The Korean Journal of Physiology and Pharmacology 2024;28(5):457-467
Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.
6.Relationship Between Amyloid Positivity and Sleep Characteristics in the Elderly With Subjective Cognitive Decline
Kyung Joon JO ; SeongHee HO ; Yun Jeong HONG ; Jee Hyang JEONG ; SangYun KIM ; Min Jeong WANG ; Seong Hye CHOI ; SeungHyun HAN ; Dong Won YANG ; Kee Hyung PARK
Dementia and Neurocognitive Disorders 2024;23(1):22-29
Background:
and Purpose: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a progressive decline in cognition and performance of daily activities. Recent studies have attempted to establish the relationship between AD and sleep. It is believed that patients with AD pathology show altered sleep characteristics years before clinical symptoms appear. This study evaluated the differences in sleep characteristics between cognitively asymptomatic patients with and without some amyloid burden.
Methods:
Sleep characteristics of 76 subjects aged 60 years or older who were diagnosed with subjective cognitive decline (SCD) but not mild cognitive impairment (MCI) or AD were measured using Fitbit ® Alta HR, a wristwatch-shaped wearable device. Amyloid deposition was evaluated using brain amyloid plaque load (BAPL) and global standardized uptake value ratio (SUVR) from fluorine-18 florbetaben positron emission tomography. Each component of measured sleep characteristics was analyzed for statistically significant differences between the amyloid-positive group and the amyloid-negative group.
Results:
Of the 76 subjects included in this study, 49 (64.5%) were female. The average age of the subjects was 70.72±6.09 years when the study started. 15 subjects were classified as amyloid-positive based on BAPL. The average global SUVR was 1.598±0.263 in the amyloidpositive group and 1.187±0.100 in the amyloid-negative group. Time spent in slow-wave sleep (SWS) was significantly lower in the amyloid-positive group (39.4±13.1 minutes) than in the amyloid-negative group (49.5±13.1 minutes) (p=0.009).
Conclusions
This study showed that SWS is different between the elderly SCD population with and without amyloid positivity. How SWS affects AD pathology requires further research.
7.Epidemiologic and Clinical Outcomes of Pediatric Renal Tumors in Korea: A Retrospective Analysis of The Korean Pediatric Hematology and Oncology Group (KPHOG) Data
Kyung-Nam KOH ; Jung Woo HAN ; Hyoung Soo CHOI ; Hyoung Jin KANG ; Ji Won LEE ; Keon Hee YOO ; Ki Woong SUNG ; Hong Hoe KOO ; Kyung Taek HONG ; Jung Yoon CHOI ; Sung Han KANG ; Hyery KIM ; Ho Joon IM ; Seung Min HAHN ; Chuhl Joo LYU ; Hee-Jo BAEK ; Hoon KOOK ; Kyung Mi PARK ; Eu Jeen YANG ; Young Tak LIM ; Seongkoo KIM ; Jae Wook LEE ; Nack-Gyun CHUNG ; Bin CHO ; Meerim PARK ; Hyeon Jin PARK ; Byung-Kiu PARK ; Jun Ah LEE ; Jun Eun PARK ; Soon Ki KIM ; Ji Yoon KIM ; Hyo Sun KIM ; Youngeun MA ; Kyung Duk PARK ; Sang Kyu PARK ; Eun Sil PARK ; Ye Jee SHIM ; Eun Sun YOO ; Kyung Ha RYU ; Jae Won YOO ; Yeon Jung LIM ; Hoi Soo YOON ; Mee Jeong LEE ; Jae Min LEE ; In-Sang JEON ; Hye Lim JUNG ; Hee Won CHUEH ; Seunghyun WON ;
Cancer Research and Treatment 2023;55(1):279-290
Purpose:
Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea.
Materials and Methods:
From January 2001 to December 2015, data of pediatric patients (0–18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed.
Results:
Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001).
Conclusion
The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.
8.Study Design and Baseline Results in a Cohort Study to Identify Predictors for the Clinical Progression to Mild Cognitive Impairment or Dementia From Subjective Cognitive Decline (CoSCo) Study
SeongHee HO ; Yun Jeong HONG ; Jee Hyang JEONG ; Kee Hyung PARK ; SangYun KIM ; Min Jeong WANG ; Seong Hye CHOI ; SeungHyun HAN ; Dong Won YANG
Dementia and Neurocognitive Disorders 2022;21(4):147-161
Background:
and Purpose: Subjective cognitive decline (SCD) refers to the self-perception of cognitive decline with normal performance on objective neuropsychological tests. SCD, which is the first help-seeking stage and the last stage before the clinical disease stage, can be considered to be the most appropriate time for prevention and treatment. This study aimed to compare characteristics between the amyloid positive and amyloid negative groups of SCD patients.
Methods:
A cohort study to identify predictors for the clinical progression to mild cognitive impairment (MCI) or dementia from subjective cognitive decline (CoSCo) study is a multicenter, prospective observational study conducted in the Republic of Korea. In total, 120 people aged 60 years or above who presented with a complaint of persistent cognitive decline were selected, and various risk factors were measured among these participants.Continuous variables were analyzed using the Wilcoxon rank-sum test, and categorical variables were analyzed using the χ2 test or Fisher’s exact test. Logistic regression models were used to assess the predictors of amyloid positivity.
Results:
The multivariate logistic regression model indicated that amyloid positivity on PET was related to a lack of hypertension, atrophy of the left temporal lateral and entorhinal cortex, low body mass index, low waist circumference, less body and visceral fat, fast gait speed, and the presence of the apolipoprotein E ε4 allele in amnestic SCD patients.
Conclusions
The CoSCo study is still in progress, and the authors aim to identify the risk factors that are related to the progression of MCI or dementia in amnestic SCD patients through a two-year follow-up longitudinal study.
9.Validity of the Clinical Frailty Scale in Korean older patients at a geriatric clinic
Hee-Won JUNG ; Il-Young JANG ; Ji Yeon BACK ; Seunghyun PARK ; Chan MI PARK ; Seung Jun HAN ; Eunju LEE
The Korean Journal of Internal Medicine 2021;36(5):1242-1250
Background/Aims:
We aimed to assess the validity of the Korean translated version of the Clinical Frailty Scale (CFS) in determining the frailty status in geriatric outpatients.
Methods:
The records of 123 ambulatory outpatients who had undergone CFS and comprehensive geriatric assessments (CGAs) including measurements for the Cardiovascular Health Study (CHS) frailty scale and the frailty index (CGA-FI) were analyzed. Correlations between CFS, CHS frailty scale, and CGA-FI were assessed. The ability of CFS to classify frailty status was calculated using the CHS frailty scale and CGA-FI as references.
Results:
The mean CFS score was 3.2 in the study population, with a mean age of 77.49 years (45.5% men). Individuals with higher CFS scores were older, had a greater burden of chronic diseases, and worse daily functions and cognitive performance. CFS scores positively correlated with CGA-FI (B = 0.78, p < 0.001) and CHS frailty scale (B = 0.67, p < 0.001) scores. For CFS, C-statistics to classify frailty by CGA-FI and CHS scale were 0.905 and 0.826, respectively. The cut-off value of CFS ≥ 4 maximized Youden’s J to classify frailty by both the CHS scale and CGAFI.
Conclusions
The CFS is a valid screening tool to assess the frailty status in outpatients of a geriatric clinic in Korea. As a simple and quick measure, the CFS may facilitate frailty assessments in real-world clinical practice.
10.Validity of the Clinical Frailty Scale in Korean older patients at a geriatric clinic
Hee-Won JUNG ; Il-Young JANG ; Ji Yeon BACK ; Seunghyun PARK ; Chan MI PARK ; Seung Jun HAN ; Eunju LEE
The Korean Journal of Internal Medicine 2021;36(5):1242-1250
Background/Aims:
We aimed to assess the validity of the Korean translated version of the Clinical Frailty Scale (CFS) in determining the frailty status in geriatric outpatients.
Methods:
The records of 123 ambulatory outpatients who had undergone CFS and comprehensive geriatric assessments (CGAs) including measurements for the Cardiovascular Health Study (CHS) frailty scale and the frailty index (CGA-FI) were analyzed. Correlations between CFS, CHS frailty scale, and CGA-FI were assessed. The ability of CFS to classify frailty status was calculated using the CHS frailty scale and CGA-FI as references.
Results:
The mean CFS score was 3.2 in the study population, with a mean age of 77.49 years (45.5% men). Individuals with higher CFS scores were older, had a greater burden of chronic diseases, and worse daily functions and cognitive performance. CFS scores positively correlated with CGA-FI (B = 0.78, p < 0.001) and CHS frailty scale (B = 0.67, p < 0.001) scores. For CFS, C-statistics to classify frailty by CGA-FI and CHS scale were 0.905 and 0.826, respectively. The cut-off value of CFS ≥ 4 maximized Youden’s J to classify frailty by both the CHS scale and CGAFI.
Conclusions
The CFS is a valid screening tool to assess the frailty status in outpatients of a geriatric clinic in Korea. As a simple and quick measure, the CFS may facilitate frailty assessments in real-world clinical practice.

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