1.DWN12088, A Prolyl-tRNA Synthetase Inhibitor, Alleviates Hepatic Injury in Nonalcoholic Steatohepatitis
Dong-Keon LEE ; Su Ho JO ; Eun Soo LEE ; Kyung Bong HA ; Na Won PARK ; Deok-Hoon KONG ; Sang-In PARK ; Joon Seok PARK ; Choon Hee CHUNG
Diabetes & Metabolism Journal 2024;48(1):97-111
Background:
Nonalcoholic steatohepatitis (NASH) is a liver disease caused by obesity that leads to hepatic lipoapoptosis, resulting in fibrosis and cirrhosis. However, the mechanism underlying NASH is largely unknown, and there is currently no effective therapeutic agent against it. DWN12088, an agent used for treating idiopathic pulmonary fibrosis, is a selective prolyl-tRNA synthetase (PRS) inhibitor that suppresses the synthesis of collagen. However, the mechanism underlying the hepatoprotective effect of DWN12088 is not clear. Therefore, we investigated the role of DWN12088 in NASH progression.
Methods:
Mice were fed a chow diet or methionine-choline deficient (MCD)-diet, which was administered with DWN12088 or saline by oral gavage for 6 weeks. The effects of DWN12088 on NASH were evaluated by pathophysiological examinations, such as real-time quantitative reverse transcription polymerase chain reaction, immunoblotting, biochemical analysis, and immunohistochemistry. Molecular and cellular mechanisms of hepatic injury were assessed by in vitro cell culture.
Results:
DWN12088 attenuated palmitic acid (PA)-induced lipid accumulation and lipoapoptosis by downregulating the Rho-kinase (ROCK)/AMP-activated protein kinase (AMPK)/sterol regulatory element-binding protein-1c (SREBP-1c) and protein kinase R-like endoplasmic reticulum kinase (PERK)/α subunit of eukaryotic initiation factor 2 (eIF2α)/activating transcription factor 4 (ATF4)/C/EBP-homologous protein (CHOP) signaling cascades. PA increased but DWN12088 inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 (Ser536, Ser276) and the expression of proinflammatory genes. Moreover, the DWN12088 inhibited transforming growth factor β (TGFβ)-induced pro-fibrotic gene expression by suppressing TGFβ receptor 1 (TGFβR1)/Smad2/3 and TGFβR1/glutamyl-prolyl-tRNA synthetase (EPRS)/signal transducer and activator of transcription 6 (STAT6) axis signaling. In the case of MCD-diet-induced NASH, DWN12088 reduced hepatic steatosis, inflammation, and lipoapoptosis and prevented the progression of fibrosis.
Conclusion
Our findings provide new insights about DWN12088, namely that it plays an important role in the overall improvement of NASH. Hence, DWN12088 shows great potential to be developed as a new integrated therapeutic agent for NASH.
2.Contemporary Statistics of Acute Ischemic Stroke and Transient Ischemic Attack in 2021: Insights From the CRCS-K-NIH Registry
Do Yeon KIM ; Tai Hwan PARK ; Yong-Jin CHO ; Jong-Moo PARK ; Kyungbok LEE ; Minwoo LEE ; Juneyoung LEE ; Sang Yoon BAE ; Da Young HONG ; Hannah JUNG ; Eunvin KO ; Hyung Seok GUK ; Beom Joon KIM ; Jun Yup KIM ; Jihoon KANG ; Moon-Ku HAN ; Sang-Soon PARK ; Keun-Sik HONG ; Hong-Kyun PARK ; Jeong-Yoon LEE ; Byung-Chul LEE ; Kyung-Ho YU ; Mi Sun OH ; Dong-Eog KIM ; Dong-Seok GWAK ; Soo Joo LEE ; Jae Guk KIM ; Jun LEE ; Doo Hyuk KWON ; Jae-Kwan CHA ; Dae-Hyun KIM ; Joon-Tae KIM ; Kang-Ho CHOI ; Hyunsoo KIM ; Jay Chol CHOI ; Joong-Goo KIM ; Chul-Hoo KANG ; Sung-il SOHN ; Jeong-Ho HONG ; Hyungjong PARK ; Sang-Hwa LEE ; Chulho KIM ; Dong-Ick SHIN ; Kyu Sun YUM ; Kyusik KANG ; Kwang-Yeol PARK ; Hae-Bong JEONG ; Chan-Young PARK ; Keon-Joo LEE ; Jee Hyun KWON ; Wook-Joo KIM ; Ji Sung LEE ; Hee-Joon BAE ;
Journal of Korean Medical Science 2024;39(34):e278-
This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively.Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques.There has been a decrease in intravenous thrombolysis rates, from 12% in 2017–2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for noncardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.
3.Myxoma of Nasal Ala in an Adult Patient
Bong-Jin SHIN ; Keon Woo PARK ; Dong Hoon LEE ; Sang Chul LIM
Korean Journal of Otolaryngology - Head and Neck Surgery 2023;66(1):50-53
Myxoma most commonly occurs in the atria, but is rare in the nasal cavity. A 58-year-old male patient presented with a nasal mass. We used endoscopic endonasal approach for treatment, and the patient was finally diagnosed with nasal ala myxoma. We report here a rare case of a patient with nasal ala myxoma along with a literature review.
4.Prasugrel-based De-Escalation of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With STEMI
You-Jeong KI ; Bong Ki LEE ; Kyung Woo PARK ; Jang-Whan BAE ; Doyeon HWANG ; Jeehoon KANG ; Jung-Kyu HAN ; Han-Mo YANG ; Hyun-Jae KANG ; Bon-Kwon KOO ; Dong-Bin KIM ; In-Ho CHAE ; Keon-Woong MOON ; Hyun Woong PARK ; Ki-Bum WON ; Dong Woon JEON ; Kyoo-Rok HAN ; Si Wan CHOI ; Jae Kean RYU ; Myung Ho JEONG ; Kwang Soo CHA ; Hyo-Soo KIM ; On behalf of the HOST-RP-ACS investigators
Korean Circulation Journal 2022;52(4):304-319
Background and Objectives:
De-escalation of dual-antiplatelet therapy through dose reduction of prasugrel improved net adverse clinical events (NACEs) after acute coronary syndrome (ACS), mainly through the reduction of bleeding without an increase in ischemic outcomes. Whether the benefits of de-escalation are sustained in highly thrombotic conditions such as ST-elevation myocardial infarction (STEMI) is unknown. We aimed to assess the efficacy and safety of de-escalation therapy in patients with STEMI or non-STsegment elevation ACS (NSTE-ACS).
Methods:
This is a pre-specified subgroup analysis of the HOST-REDUCE-POLYTECH-ACS trial. ACS patients were randomized to prasugrel de-escalation (5 mg daily) or conventional dose (10 mg daily) at 1-month post-percutaneous coronary intervention. The primary endpoint was a NACE, defined as a composite of all-cause death, non-fatal myocardial infarction, stent thrombosis, clinically driven revascularization, stroke, and bleeding events of grade ≥2 Bleeding Academic Research Consortium (BARC) criteria at 1 year.
Results:
Among 2,338 patients included in the randomization, 326 patients were diagnosed with STEMI. In patients with NSTE-ACS, the risk of the primary endpoint was significantly reduced with de-escalation (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.48– 0.89; p=0.006 for de-escalation vs. conventional), mainly driven by a reduced bleeding. However, in those with STEMI, there was no difference in the occurrence of the primary outcome (HR, 1.04; 95% CI, 0.48–2.26; p=0.915; p for interaction=0.271).
Conclusions
Prasugrel dose de-escalation reduced the rate of NACE and bleeding, without increasing the rate of ischemic events in NSTE-ACS patients but not in STEMI patients.
5.Erratum: Correction of Text in the Article “Prasugrel-based De-Escalation of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With STEMI”
You-Jeong KI ; Bong Ki LEE ; Kyung Woo PARK ; Jang-Whan BAE ; Doyeon HWANG ; Jeehoon KANG ; Jung-Kyu HAN ; Han-Mo YANG ; Hyun-Jae KANG ; Bon-Kwon KOO ; Dong-Bin KIM ; In-Ho CHAE ; Keon-Woong MOON ; Hyun Woong PARK ; Ki-Bum WON ; Dong Woon JEON ; Kyoo-Rok HAN ; Si Wan CHOI ; Jae Kean RYU ; Myung Ho JEONG ; Kwang Soo CHA ; Hyo-Soo KIM ;
Korean Circulation Journal 2022;52(6):483-484
6.Occurrence of a Hybrid Between Taenia saginata and Taenia asiatica Tapeworms in Cambodia
Taehee CHANG ; Bong-Kwang JUNG ; Sooji HONG ; Hyejoo SHIN ; Seungwan RYOO ; Jeonggyu LEE ; Keon Hoon LEE ; Hansol PARK ; Keeseon S. EOM ; Virak KHIEU ; Rekol HUY ; Woon-Mok SOHN ; Jong-Yil CHAI
The Korean Journal of Parasitology 2021;59(2):179-182
Human infection with Taenia asiatica or a hybrid between Taenia saginata and T. asiatica has not been reported in Cambodia. We detected for the first time a hybrid form between T. saginata and T. asiatica in Preah Vihear Province, Cambodia. An adult tapeworm specimen, i.e., 75 cm long strobila without scolex, was expelled from a 27-year-old man after praziquantel medication and purging. It was morphologically indistinguishable between T. saginata and T. asiatica. Several proglottids were molecularly analyzed to confirm the tapeworm species. The mitochondrial gene encoding cytochrome c oxidase subunit 1 (cox1) and nuclear genes encoding elongation factor-1α (ef1) and ezrin-radixin-moesin (ERM)-like protein (elp) were sequenced, and a single-allele analysis was performed to confirm the haploid genotype. The results revealed that our sample showed a discrepancy between the mitochondrial and 2 nuclear genes. It possessed homozygous sequences typical of T. saginata at cox1 and ef1 loci. However, it was heterozygous at the elp locus, with 1 allele in T. asiatica (elpA) and 1 in T. saginata (elpC), which indicates that it is a hybrid between T. saginata and T. asiatica. The present results confirmed the presence of a hybrid between T. saginata and T. asiatica in Cambodia and strongly suggest the existence of also ‘pure’ T. asiatica in Cambodia.
7.Enterobius vermicularis Infection among Preschool Children: A 12-Year (2008-2019) Survey in Large Cities and Provinces of the Republic of Korea
Hyejoo SHIN ; Bong-Kwang JUNG ; Seungwan RYOO ; Sooji HONG ; Taehee CHANG ; Jiyeon PARK ; Keon Hoon LEE ; Jeonggyu LEE ; Jae Young PARK ; Hoo-Gn JEOUNG ; Jae Hyun CHO ; Jong-Yil CHAI
The Korean Journal of Parasitology 2021;59(4):421-426
A 12-year nationwide survey (2008-2019) was performed to investigate the prevalence of Enterobius vermicularis infection among preschool children in Seoul, 4 large cites (Busan, Incheon, Daegu, and Ulsan), and 9 provinces (grouped into 5 localities) in the Republic of Korea (=Korea). The survey was carried out once a year by 16 regional offices of the Korea Association of Health Promotion. The cello-tape perianal swab method (1 smear per child) was applied to detect eggs of E. vermicularis and other helminths. According to the results, the egg positive rate of E. vermicularis infection in 2008-2009 was 1.8-2.0%, but it decreased gradually to 0.6% in 2019 (P<0.05). The prevalence was significantly higher in boys (0.7-5.0%, mean 1.8%) than in girls (0.5-2.8%, mean 1.3%) (P<0.05). The 2 most southern localities, Jejudo (Province) and Jeolla-do (inclusive of Jeollabuk-do and Jeollanam-do) and a mid-western province, Gyeonggi-do, revealed higher prevalences, whereas Seoul and Gangwon-do showed lower prevalences. The results indicate that a low-grade prevalence of E. vermicularis infection (less than 4%) has been maintained for the recent 12 years among preschool children in Korea. Continuous monitoring of enterobiasis in the child age group is necessary in Korea.
8.Occurrence of a Hybrid Between Taenia saginata and Taenia asiatica Tapeworms in Cambodia
Taehee CHANG ; Bong-Kwang JUNG ; Sooji HONG ; Hyejoo SHIN ; Seungwan RYOO ; Jeonggyu LEE ; Keon Hoon LEE ; Hansol PARK ; Keeseon S. EOM ; Virak KHIEU ; Rekol HUY ; Woon-Mok SOHN ; Jong-Yil CHAI
The Korean Journal of Parasitology 2021;59(2):179-182
Human infection with Taenia asiatica or a hybrid between Taenia saginata and T. asiatica has not been reported in Cambodia. We detected for the first time a hybrid form between T. saginata and T. asiatica in Preah Vihear Province, Cambodia. An adult tapeworm specimen, i.e., 75 cm long strobila without scolex, was expelled from a 27-year-old man after praziquantel medication and purging. It was morphologically indistinguishable between T. saginata and T. asiatica. Several proglottids were molecularly analyzed to confirm the tapeworm species. The mitochondrial gene encoding cytochrome c oxidase subunit 1 (cox1) and nuclear genes encoding elongation factor-1α (ef1) and ezrin-radixin-moesin (ERM)-like protein (elp) were sequenced, and a single-allele analysis was performed to confirm the haploid genotype. The results revealed that our sample showed a discrepancy between the mitochondrial and 2 nuclear genes. It possessed homozygous sequences typical of T. saginata at cox1 and ef1 loci. However, it was heterozygous at the elp locus, with 1 allele in T. asiatica (elpA) and 1 in T. saginata (elpC), which indicates that it is a hybrid between T. saginata and T. asiatica. The present results confirmed the presence of a hybrid between T. saginata and T. asiatica in Cambodia and strongly suggest the existence of also ‘pure’ T. asiatica in Cambodia.
9.Enterobius vermicularis Infection among Preschool Children: A 12-Year (2008-2019) Survey in Large Cities and Provinces of the Republic of Korea
Hyejoo SHIN ; Bong-Kwang JUNG ; Seungwan RYOO ; Sooji HONG ; Taehee CHANG ; Jiyeon PARK ; Keon Hoon LEE ; Jeonggyu LEE ; Jae Young PARK ; Hoo-Gn JEOUNG ; Jae Hyun CHO ; Jong-Yil CHAI
The Korean Journal of Parasitology 2021;59(4):421-426
A 12-year nationwide survey (2008-2019) was performed to investigate the prevalence of Enterobius vermicularis infection among preschool children in Seoul, 4 large cites (Busan, Incheon, Daegu, and Ulsan), and 9 provinces (grouped into 5 localities) in the Republic of Korea (=Korea). The survey was carried out once a year by 16 regional offices of the Korea Association of Health Promotion. The cello-tape perianal swab method (1 smear per child) was applied to detect eggs of E. vermicularis and other helminths. According to the results, the egg positive rate of E. vermicularis infection in 2008-2009 was 1.8-2.0%, but it decreased gradually to 0.6% in 2019 (P<0.05). The prevalence was significantly higher in boys (0.7-5.0%, mean 1.8%) than in girls (0.5-2.8%, mean 1.3%) (P<0.05). The 2 most southern localities, Jejudo (Province) and Jeolla-do (inclusive of Jeollabuk-do and Jeollanam-do) and a mid-western province, Gyeonggi-do, revealed higher prevalences, whereas Seoul and Gangwon-do showed lower prevalences. The results indicate that a low-grade prevalence of E. vermicularis infection (less than 4%) has been maintained for the recent 12 years among preschool children in Korea. Continuous monitoring of enterobiasis in the child age group is necessary in Korea.
10.Real-World Experience of Nivolumab in Non-small Cell Lung Cancer in Korea
Sun Min LIM ; Sang-We KIM ; Byoung Chul CHO ; Jin Hyung KANG ; Myung-Ju AHN ; Dong-Wan KIM ; Young-Chul KIM ; Jin Soo LEE ; Jong-Seok LEE ; Sung Yong LEE ; Keon Uk PARK ; Ho Jung AN ; Eun Kyung CHO ; Tae Won JANG ; Bong-Seog KIM ; Joo-Hang KIM ; Sung Sook LEE ; Im-II NA ; Seung Soo YOO ; Ki Hyeong LEE
Cancer Research and Treatment 2020;52(4):1112-1119
Purpose:
The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program.
Materials and Methods:
Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected.
Results:
Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data.
Conclusion
This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

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