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.Multiplex Real-Time Polymerase Chain Reaction Analysis of Pathogens in Peri-Implantitis and Periodontitis: A Randomized Trial
Journal of Dental Hygiene Science 2024;24(2):97-106
Background:
Periodontitis and peri-implantitis are diseases caused by pathogenic microorganisms that cause tissue damage and alveolar bone destruction resulting in the loss of teeth and implants. Due to the biological differences in the tissues surrounding the implants, peri-implantitis progresses more rapidly and intensely than periodontitis, underscoring the importance of understanding the characteristics and interactions of pathogenic bacteria. This study aimed to quantitatively analyze the pathogenic microorganisms associated with periodontitis and peri-implantitis in Korean patients and evaluate the correlation between these bacteria.
Methods:
A total of 98 (52 males and 46 females) were randomly selected and classified into three groups (healthy group [HG]=25; periodontitis group [PG]=31; and peri-implantitis group [PIG]=42). The relative expression levels of 11 pathogenic microorganisms collected from the gingival sulcus fluid were determined using multiplex real-time polymerase chain reaction.
Results:
Eikenella corrodens, Fusobacterium nucleatum, and Prevotella nigrescens were highly prevalent in the HG, PG, and PIG patients. The results of the relative quantitative analysis of microorganisms showed that all bacteria belonging to the green, orange, and red complexes were significantly more abundant in the PG and PIG than in the HG (p<0.05). Porphyromonas gingivalis in the red complex showed a positive correlation with all microorganisms in the orange complex (p<0.05).Campylobacter rectus in the orange complex showed a significant positive correlation with all microorganisms in the red complex, and with F. nucleatum, P. nigrescens, Prevotella intermedia, and Eubacterium nodatum (p<0.05).
Conclusion
P. gingivalis, C. rectus, and F. nucleatum exhibit strong interactions. Removing these bacteria can block complex formation and enhance the prevention and treatment of periodontitis and peri-implantitis.
3.Case of Chronic Active Epstein-Barr Virus Infection Developed Hemophagocytic Lymphohistiocytosis after COVID-19 Infection
Sumin JO ; Hye Lim JUNG ; Sooyeon LIM ; Eun Sil KIM ; Aram YANG ; Ji Hee KWAK ; Deok Soo KIM ; Jung Yeon SHIM ; Jae Won SHIM
Clinical Pediatric Hematology-Oncology 2023;30(2):80-84
In children, prolonged primary Epstein-Barr virus (EBV) infection or reactivation may lead to the development of T or natural killer cell lymphoproliferative disorders, classified as chronic active EBV infection (CAEBV). CAEBV is a prolonged systemic illness lasting beyond three months, with elevated EBV DNA levels in the serum or affected tissue and a lack of underlying immunodeficiency. Notably, EBV is the most common virus that induces secondary hemophagocytic lymphohistiocytosis (HLH), and Coronavirus disease 2019 (COVID-19) has been reported to trigger HLH. We present the case of a 20-year-old Korean male who was diagnosed with CAEBV and developed HLH after being infected with COVID-19. The patient met 7 out of 8 criteria for HLH. Following treatment with corticosteroids and intravenous immunoglobulin, the patient recovered from HLH without additional chemotherapy. HLH treatment should be tailored to each patient based on clinical presentation and disease severity.Prolonged and regular evaluation for developing HLH or lymphoma is necessary for patients with CAEBV.
4.Effects of Professional Toothbrushing and Instruction in the Elderly: A Randomized Trial.
Eun Deok JO ; Eun Sol KIM ; Hae Kyung HONG ; Gyeong Soon HAN
Journal of Dental Hygiene Science 2018;18(5):305-311
The purpose of this study was to identify the effect of providing toothbrushing by professionals as part of oral hygiene education for the elderly. We randomly visited 12 centers in the metropolitan city and analyzed the data of 114 participants among 310 early registrants aged >65 years, who participated in the study at all 3 time points. The subjects were categorized into an experimental group (odd-numbered visits) and a control group (even-numbered visits). Oral hygiene practices were provided for both experimental and control groups, but professional toothbrushing was performed in a different manner in the experimental group. Differences in plaque index (PI) according to the subjects' general characteristics and oral health status were assessed using the t-test, and the effect of PI difference between the experimental and control groups was assessed by repeated measure two-way analysis of variance. A stepwise multiple regression analysis was used to analyze factors affecting the PI. At baseline, the mean overall PI was 61.82. In both experimental and control groups, the PI significantly reduced from the baseline (p <0.01). At 5 weeks, the experimental group showed a decrease of 27.16 points from the baseline, and the 10-week PI was similar to the 5-week PI. The control group showed a decrease of 14.87 points from the baseline, and the PI increased by 5.74 points at 10 weeks. PI-related factors were gender and self-xerostomia. The PI was lower in the female group and the group with self-xerostomia (p <0.01). It is important to select an appropriate method to educate elderly subjects on proper removal of dental plaque and to habituate correct behavior, which requires inclusion of a direct toothbrushing intervention by a specialist.
Aged*
;
Dental Plaque
;
Education
;
Female
;
Humans
;
Methods
;
Oral Health
;
Oral Hygiene
;
Specialization
;
Toothbrushing*
5.Multidisciplinary Approach to Decrease In-Hospital Delay for Stroke Thrombolysis.
Sang Beom JEON ; Seung Mok RYOO ; Deok Hee LEE ; Sun U KWON ; Seongsoo JANG ; Eun Jae LEE ; Sang Hun LEE ; Jung Hee HAN ; Mi Jeong YOON ; Soo JEONG ; Young Uk CHO ; Sungyang JO ; Seung Bok LIM ; Joong Goo KIM ; Han Bin LEE ; Seung Chai JUNG ; Kye Won PARK ; Min Hwan LEE ; Dong Wha KANG ; Dae Chul SUH ; Jong S KIM
Journal of Stroke 2017;19(2):196-204
BACKGROUND AND PURPOSE: Decreasing the time delay for thrombolysis, including intravenous thrombolysis (IVT) with tissue plasminogen activator and intra-arterial thrombectomy (IAT), is critical for decreasing the morbidity and mortality of patients experiencing acute stroke. We aimed to decrease the in-hospital delay for both IVT and IAT through a multidisciplinary approach that is feasible 24 h/day. METHODS: We implemented the Stroke Alert Team (SAT) on May 2, 2016, which introduced hospital-initiated ambulance prenotification and reorganized in-hospital processes. We compared the patient characteristics, time for each step of the evaluation and thrombolysis, thrombolysis rate, and post-thrombolysis intracranial hemorrhage from January 2014 to August 2016. RESULTS: A total of 245 patients received thrombolysis (198 before SAT; 47 after SAT). The median door-to-CT, door-to-MRI, and door-to-laboratory times decreased to 13 min, 37.5 min, and 8 min, respectively, after SAT implementation (P<0.001). The median door-to-IVT time decreased from 46 min (interquartile range [IQR] 36–57 min) to 20.5 min (IQR 15.8–32.5 min; P<0.001). The median door-to-IAT time decreased from 156 min (IQR 124.5–212.5 min) to 86.5 min (IQR 67.5–102.3 min; P<0.001). The thrombolysis rate increased from 9.8% (198/2,012) to 15.8% (47/297; P=0.002), and the post-thrombolysis radiological intracranial hemorrhage rate decreased from 12.6% (25/198) to 2.1% (1/47; P=0.035). CONCLUSIONS: SAT significantly decreased the in-hospital delay for thrombolysis, increased thrombolysis rate, and decreased post-thrombolysis intracranial hemorrhage. Time benefits of SAT were observed for both IVT and IAT and during office hours and after-hours.
Ambulances
;
Cerebral Infarction
;
Humans
;
Intracranial Hemorrhages
;
Mortality
;
Stroke*
;
Thrombectomy
;
Thrombolytic Therapy
;
Tissue Plasminogen Activator
6.Bench-top Comparison of Physical Properties of 4 Commercially-Available Self-Expanding Intracranial Stents.
Su Hee CHO ; Won Il JO ; Ye Eun JO ; Ku Hyun YANG ; Jung Cheol PARK ; Deok Hee LEE
Neurointervention 2017;12(1):31-39
PURPOSE: To better understand the performance of four commercially available neurovascular stents in intracranial aneurysm embolization, the stents were compared in terms of their basic morphological and mechanical properties. MATERIALS AND METHODS: Four different types of stents that are currently being used for cerebral aneurysm embolization were prepared (two stents per type). Two were laser-cut stents (Neuroform and Enterprise) and two were braided from a single nitinol wire (LEO and LVIS stents). All were subjected to quantitative measurements of stent size, pore density, metal coverage, the force needed to load, push, and deploy the stent, radial force on deployment, surface roughness, and corrosion resistance. RESULTS: Compared to their nominal diameters, all stents had greater diameters after deployment. The length generally decreased after deployment. This was particularly marked in the braided stents. The braided stents also had higher pore densities than the laser-cut stents. Metal coverage was highest in the LEO stent (14%) and lowest in the Enterprise stent (5%). The LIVS stent had the highest microcatheter loading force (81.5 gf). The LEO stent had the highest passage force (55.0 gf) and deployment force (78.9 gf). The LVIS and LEO stents had the highest perpendicular (37.1 gf) and circumferential (178.4 gf) radial forces, respectively. The Enterprise stent had the roughest stent wire, followed by the LVIS, LEO, and Neuroform stents. CONCLUSION: The four neurovascular stent types differed in terms of morphological and physical characteristics. An understanding of this diversity may help to decide which stent is most suitable for specific clinical situations.
Corrosion
;
Intracranial Aneurysm
;
Stents*
7.In Vitro Quantification of the Radiopacity of Onyx during Embolization.
Yuan Yuan JIANG ; Ye Eun JO ; Jung Min WOO ; Ok Kyun LIM ; Changmo HWANG ; Jun Young MAENG ; Jieun KIM ; Namkug KIM ; Deok Hee LEE
Neurointervention 2017;12(1):3-10
PURPOSE: Onyx has been successfully applied in the treatment of various neurovascular lesions. However, some experience is required to get accustomed to its unpredictable fluoroscopic visibility during injection. This in vitro study aimed to evaluate the characteristics of radiopacity change in a simulated embolization procedure. MATERIALS AND METHODS: Using a bench-top Onyx injection experiment simulating a typical brain arteriovenous malformation embolization, nine cycles of casting modes (continuous injection) and plugging modes (injection with intermittent pauses) were performed. Radiodensity of Onyx droplets collected from the microcatheter tip and the distal head portion of the microcatheter were measured as time lapsed. Distribution of droplet radiodensity (radiodensity) and distribution of radiographic grade (grade) were analyzed and compared by repeated measurements. RESULTS: Within-group analysis revealed no significant radiodensity change with time (P>0.05). The radiodensity was significantly higher in the casting mode than in the plugging mode (P<0.01). The lateral radiograph of the microcatheter showed higher radiopacity (P<0.01) and better evenness (P<0.01) in the casting mode than in the plugging mode. A significant difference in microcatheter attenuation (both radiographic grade mean and SD; P<0.01) was noted between the two modes. Radiodensity had a significant influence on the radiopacity and radiopacity evenness of the microcatheter. CONCLUSION: The radiopacity of the Onyx can vary significantly over time because of early precipitation of tantalum powder. Radiopacity decreased significantly during plugging modes, characterized by pauses between injections.
Arteriovenous Malformations
;
Brain
;
Head
;
In Vitro Techniques*
;
Tantalum
8.Enlarged Parent Artery Lumen at Aneurysmal-Neck Segment in Wide-Necked Distal Internal Carotid Artery Aneurysms.
Jong Won LEE ; Jung Min WOO ; Ok Kyun LIM ; Ye Eun JO ; Jae Kyun KIM ; Eun Sang KIM ; Deok Hee LEE
Neurointervention 2015;10(2):82-88
PURPOSE: Hypothesizing that the parent artery (PA) diameter of the aneurysm-neck segment is larger than those of normal segments, especially in wide-necked aneurysm cases, we conducted 3D angiographic analyses in wide-necked aneurysm cases focusing on the luminal morphologic change of the PA. MATERIALS AND METHODS: Under the approval of local IRB, we enrolled 26 patients with distal internal carotid artery (ICA) aneurysms, which were treated with stent assisted coiling. The PA diameters along the centerline were measured at 6 points with built-in software by two observers. Those 6 points were P1 and P2 proximally, P3 and P4 at the aneurysm ostium margins, and P5 and P6 distally. We performed an ANOVA test and a Bonferroni method for post hoc analyses. Linear regression analysis was performed to find any morphologic influencing factors. RESULTS: There were 20 distal ICA aneurysms out of 26 consecutive cases after exclusion. The differences in diameter at each point were statistically significant (p<0.0001). On post hoc analyses, the difference between P4 and P5 was significant both in maximum and mean PA diameters (p<0.0001 and p<0.001, respectively). Multivariate analyses failed to reveal any morphological influencing factor. CONCLUSION: PAs harboring a wide-necked aneurysm requiring stent assistance for coiling showed significant enlargement of the lumen, especially at the distal transition segment of the aneurysm ostium and the PA.
Aneurysm*
;
Arteries*
;
Carotid Artery, Internal*
;
Cerebral Angiography
;
Ethics Committees, Research
;
Humans
;
Intracranial Aneurysm
;
Linear Models
;
Multivariate Analysis
;
Parents*
;
Phenobarbital
;
Stents
9.Retraction: Aortic Dissection and Rupture in a Child.
Yun Ju JO ; Eun Jeong LEE ; Jin Won OH ; Chang Min MOON ; Deok Kyu CHO ; Yun Hyeong CHO ; Ki Hyun BYUN ; Lucy Youngmin EUN
Korean Circulation Journal 2012;42(7):511-511
No abstract available.
10.Influencing factors in the halitosis.
Journal of Korean Academy of Oral Health 2012;36(4):272-281
OBJECTIVES: The aim of this study is to analyze the factors that influence adults halitosis. METHODS: The subjects of this study were 186 adults aged from 35 to 69, between April 4 and May 30, 2012. Data were analyzed with t-test, one-way ANOVA, and binary logistic regression analysis SPSS 19.0. RESULTS: The most influential factor of VSCs was halitosis perceived by others (OR: 5.18; 95% CI: 1.82-14.70), which was followed by oral respiration (OR: 3.65; 95% CI: 1.28-10.41), and O'Leary index (OR: 3.40; 95% CI: 1.55-7.46) in the order. The influential factors of ammonia were respiratory disease (OR: 30.72; 95% CI: 1.85-51.37), gastrointestinal disease (OR: 12.28; 95% CI: 1.78-44.79), missing tooth (OR: 3.75; 95% CI: 1.57-8.92), periodontal pocket (OR: 2.61; 95% CI: 1.10-6.18), tongue brushing (OR: 0.38; 95% CI: 0.15-0.95), and oral prophylaxis (within a year) (OR: 0.31; 95% CI: 0.13-0.75). CONCLUSIONS: Halitosis is the result of complex actions among individual characteristics, systematic disease, oral health state, and health behavior.
Adult
;
Aged
;
Ammonia
;
Dental Plaque Index
;
Gastrointestinal Diseases
;
Halitosis
;
Health Behavior
;
Humans
;
Logistic Models
;
Oral Health
;
Periodontal Pocket
;
Respiration
;
Tongue
;
Tooth

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