1.A Novel Histone Deacetylase 6 Inhibitor, 4-FHA, Improves Scopolamine-Induced Cognitive and Memory Impairment in Mice
Jee-Yeon SEO ; Jisoo KIM ; Yong-Hyun KO ; Bo-Ram LEE ; Kwang-Hyun HUR ; Young Hoon JUNG ; Hyun-Ju PARK ; Seok-Yong LEE ; Choon-Gon JANG
Biomolecules & Therapeutics 2025;33(2):268-277
Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.
2.A Novel Histone Deacetylase 6 Inhibitor, 4-FHA, Improves Scopolamine-Induced Cognitive and Memory Impairment in Mice
Jee-Yeon SEO ; Jisoo KIM ; Yong-Hyun KO ; Bo-Ram LEE ; Kwang-Hyun HUR ; Young Hoon JUNG ; Hyun-Ju PARK ; Seok-Yong LEE ; Choon-Gon JANG
Biomolecules & Therapeutics 2025;33(2):268-277
Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.
3.A Novel Histone Deacetylase 6 Inhibitor, 4-FHA, Improves Scopolamine-Induced Cognitive and Memory Impairment in Mice
Jee-Yeon SEO ; Jisoo KIM ; Yong-Hyun KO ; Bo-Ram LEE ; Kwang-Hyun HUR ; Young Hoon JUNG ; Hyun-Ju PARK ; Seok-Yong LEE ; Choon-Gon JANG
Biomolecules & Therapeutics 2025;33(2):268-277
Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.
4.TP53 Mutation Status in Myelodysplastic Neoplasm and Acute Myeloid Leukemia: Impact of Reclassification Based on the 5th WHO and International Consensus Classification Criteria: A Korean Multicenter Study
Hyun-Young KIM ; Saeam SHIN ; Jong-Mi LEE ; In-Suk KIM ; Boram KIM ; Hee-Jin KIM ; Yu Jeong CHOI ; Byunggyu BAE ; Yonggoo KIM ; Eunhui JI ; Hyerin KIM ; Hyerim KIM ; Jee-Soo LEE ; Yoon Hwan CHANG ; Hyun Kyung KIM ; Ja Young LEE ; Shinae YU ; Miyoung KIM ; Young-Uk CHO ; Seongsoo JANG ; Myungshin KIM
Annals of Laboratory Medicine 2025;45(2):160-169
Background:
TP53 mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize TP53-mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of TP53-mutated MDS and AML, focusing on diagnostic aspects based on updated classifications.
Methods:
This study included patients aged ≥ 18 yrs who were diagnosed as having MDS(N = 1,244) or AML (N = 2,115) at six institutions. The results of bone marrow examination, cytogenetic studies, and targeted next-generation sequencing, including TP53, were collected and analyzed.
Results:
TP53 mutations were detected in 9.3% and 9.2% of patients with MDS and AML, respectively. Missense mutation was the most common, with hotspot codons R248/ R273/G245/Y220/R175/C238 accounting for 25.4% of TP53 mutations. Ten percent of patients had multiple TP53 mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of TP53 mutations was 41.5%, with a notable difference according to the presence of a complex karyotype. According to the 5th WHO classification and ICC, the multi-hit TP53 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a TP53 VAF > 50% for the 5th WHO classification and the presence of a complex karyotype for the ICC.
Conclusions
Collectively, we elucidated the molecular genetic characteristics of patients with TP53-mutated MDS and AML, highlighting key factors in applying TP53 mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.
5.Clinical Practice Guideline for Blood-based Circulating Tumor DNA Assays
Jee-Soo LEE ; Eun Hye CHO ; Boram KIM ; Jinyoung HONG ; Young-gon KIM ; Yoonjung KIM ; Ja-Hyun JANG ; Seung-Tae LEE ; Sun-Young KONG ; Woochang LEE ; Saeam SHIN ; Eun Young SONG ;
Annals of Laboratory Medicine 2024;44(3):195-209
Circulating tumor DNA (ctDNA) has emerged as a promising tool for various clinical applications, including early diagnosis, therapeutic target identification, treatment response monitoring, prognosis evaluation, and minimal residual disease detection. Consequently, ctDNA assays have been incorporated into clinical practice. In this review, we offer an indepth exploration of the clinical implementation of ctDNA assays. Notably, we examined existing evidence related to pre-analytical procedures, analytical components in current technologies, and result interpretation and reporting processes. The primary objective of this guidelines is to provide recommendations for the clinical utilization of ctDNA assays.
6.Introduction to the forensic research via omics markers in environmental health vulnerable areas (FROM) study
Jung-Yeon KWON ; Woo Jin KIM ; Yong Min CHO ; Byoung-gwon KIM ; Seungho LEE ; Jee Hyun RHO ; Sang-Yong EOM ; Dahee HAN ; Kyung-Hwa CHOI ; Jang-Hee LEE ; Jeeyoung KIM ; Sungho WON ; Hee-Gyoo KANG ; Sora MUN ; Hyun Ju YOO ; Jung-Woong KIM ; Kwan LEE ; Won-Ju PARK ; Seongchul HONG ; Young-Seoub HONG
Epidemiology and Health 2024;46(1):e2024062-
This research group (forensic research via omics markers in environmental health vulnerable areas: FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areas—including refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matter—along with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.
7.Differences in Symptoms According to the Concordance Value Between Self-Reported Pain Sites and Standardized Palpation Pain Sites in Temporomandibular Disorder Patients: Pilot Study
Jee-Won JANG ; Seo-Young CHOI ; Yong-Woo AHN ; Sung-Hee JEONG ; Soo-Min OK ; Hye-Mi JEON ; Hye-Min JU
Journal of Oral Medicine and Pain 2024;49(3):49-56
Purpose:
The aims were to investigate potential differences in clinical assessments among acute pain-related temporomandibular disorder (TMD) with different concordance value (CV) between number of self-reported painful site (NSP) and number of painful sites on palpation (NPP), and if it makes sense to treat them differently.
Methods:
A total of 61 patients were divided into three groups according to CV: 10 patients (concordance poor [CP]), 19 patients (concordance moderate [CM]), and 32 patients (concordance high [CH]). Clinical assessments were conducted using a standardized method in diagnostic criteria for temporomandibular disorders (DC/TMD). We compared collected information including sex, diagnosis, numerical rating scale (NRS), NPP, NSP, sleep duration, DC/TMD Axis II questionnaire, and perceived stress scale among three groups.
Results:
Among the clinical assessment, NRS, sleep duration, NPP, NSP, total scores of Oral Behaviors Checklist, Patient Health Questionnaire (PHQ)-15, PHQ-9 showed significant differences among 3 groups. NRS, NPP, NSP, PHQ-15, and PHQ-9 were higher in the CP group than in the CM and CH groups. Sleep duration was positively and NPP, NRS were negatively correlated with CV.
Conclusions
While previous studies suggested differences between chronic and acute TMD in DC/TMD items, our findings propose the CV might be a key factor that could predict the severity and susceptibility of acute-TMD patients. However, Additional studies are required to determine whether their long-term prognosis was similar to that of chronic pain patients and what the response to treatment was among the three groups.
8.Introduction to the forensic research via omics markers in environmental health vulnerable areas (FROM) study
Jung-Yeon KWON ; Woo Jin KIM ; Yong Min CHO ; Byoung-gwon KIM ; Seungho LEE ; Jee Hyun RHO ; Sang-Yong EOM ; Dahee HAN ; Kyung-Hwa CHOI ; Jang-Hee LEE ; Jeeyoung KIM ; Sungho WON ; Hee-Gyoo KANG ; Sora MUN ; Hyun Ju YOO ; Jung-Woong KIM ; Kwan LEE ; Won-Ju PARK ; Seongchul HONG ; Young-Seoub HONG
Epidemiology and Health 2024;46(1):e2024062-
This research group (forensic research via omics markers in environmental health vulnerable areas: FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areas—including refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matter—along with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.
9.Introduction to the forensic research via omics markers in environmental health vulnerable areas (FROM) study
Jung-Yeon KWON ; Woo Jin KIM ; Yong Min CHO ; Byoung-gwon KIM ; Seungho LEE ; Jee Hyun RHO ; Sang-Yong EOM ; Dahee HAN ; Kyung-Hwa CHOI ; Jang-Hee LEE ; Jeeyoung KIM ; Sungho WON ; Hee-Gyoo KANG ; Sora MUN ; Hyun Ju YOO ; Jung-Woong KIM ; Kwan LEE ; Won-Ju PARK ; Seongchul HONG ; Young-Seoub HONG
Epidemiology and Health 2024;46(1):e2024062-
This research group (forensic research via omics markers in environmental health vulnerable areas: FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areas—including refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matter—along with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.
10.Introduction to the forensic research via omics markers in environmental health vulnerable areas (FROM) study
Jung-Yeon KWON ; Woo Jin KIM ; Yong Min CHO ; Byoung-gwon KIM ; Seungho LEE ; Jee Hyun RHO ; Sang-Yong EOM ; Dahee HAN ; Kyung-Hwa CHOI ; Jang-Hee LEE ; Jeeyoung KIM ; Sungho WON ; Hee-Gyoo KANG ; Sora MUN ; Hyun Ju YOO ; Jung-Woong KIM ; Kwan LEE ; Won-Ju PARK ; Seongchul HONG ; Young-Seoub HONG
Epidemiology and Health 2024;46(1):e2024062-
This research group (forensic research via omics markers in environmental health vulnerable areas: FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areas—including refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matter—along with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.

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