1.Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis
Da Som JEONG ; Ji-Young LEE ; Hyo-Jeong HAN ; Soo Min KO ; Dong Hyun LEE ; Yerin LEE ; Young-Sik PARK ; Byong-Cheol SHIN ; Woo-Chan SON
The Korean Journal of Physiology and Pharmacology 2025;29(2):179-189
Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.
2.Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis
Da Som JEONG ; Ji-Young LEE ; Hyo-Jeong HAN ; Soo Min KO ; Dong Hyun LEE ; Yerin LEE ; Young-Sik PARK ; Byong-Cheol SHIN ; Woo-Chan SON
The Korean Journal of Physiology and Pharmacology 2025;29(2):179-189
Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.
3.Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis
Da Som JEONG ; Ji-Young LEE ; Hyo-Jeong HAN ; Soo Min KO ; Dong Hyun LEE ; Yerin LEE ; Young-Sik PARK ; Byong-Cheol SHIN ; Woo-Chan SON
The Korean Journal of Physiology and Pharmacology 2025;29(2):179-189
Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.
4.Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis
Da Som JEONG ; Ji-Young LEE ; Hyo-Jeong HAN ; Soo Min KO ; Dong Hyun LEE ; Yerin LEE ; Young-Sik PARK ; Byong-Cheol SHIN ; Woo-Chan SON
The Korean Journal of Physiology and Pharmacology 2025;29(2):179-189
Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.
5.Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis
Da Som JEONG ; Ji-Young LEE ; Hyo-Jeong HAN ; Soo Min KO ; Dong Hyun LEE ; Yerin LEE ; Young-Sik PARK ; Byong-Cheol SHIN ; Woo-Chan SON
The Korean Journal of Physiology and Pharmacology 2025;29(2):179-189
Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.
6.Efficacy and Safety of Infliximab in Intestinal Behçet’s Disease:A Multicenter, Phase 3 Study (BEGIN)
Jae Hee CHEON ; Hyun-Soo KIM ; Dong Soo HAN ; Sung Kook KIM ; Sung Jae SHIN ; Joo Sung KIM ; Byong Duk YE ; Geun Am SONG ; YoungJa LEE ; Youngdoe KIM ; Yoosun LEE ; Won Ho KIM ;
Gut and Liver 2023;17(5):777-785
Background/Aims:
To date, there is no prospective study that specifically investigated the efficacy of infliximab in intestinal Behçet’s disease (BD). This study evaluated the efficacy of infliximab in patients with moderate-to-severe active intestinal BD that are refractory to conventional therapies.
Methods:
This phase 3, interventional, open-label, single-arm study evaluated clinical outcomes of infliximab treatment in patients with moderate-to-severe intestinal BD. The coprimary endpoints were clinical response, decrease in disease activity index for intestinal BD (DAIBD) score ≥20 from weeks 0 to 8 for the induction therapy and week 32 for the maintenance therapy.
Results:
A total of 33 patients entered the induction therapy and were treated with infliximab 5 mg/kg intravenously at weeks 0, 2, and 6. The mean DAIBD score changed from 90.8±40.1 at week 0 to 40.3±36.4 at week 8, with a significant mean change of 50.5±36.4 (95% confidence interval, 37.5 to 63.4; p<0.001). Thirty-one (93.9%) continued to receive 5 mg/kg infliximab every 8 weeks during the maintenance therapy. The mean change in the DAIBD score after the maintenance therapy was statistically significant (61.5±38.5; 95% confidence interval, 46.0 to 77.1; p<0.001, from weeks 0 to 32). The proportion of patients who maintained a clinical response was 92.3% at week 32. No severe adverse reactions occurred during the induction and maintenance therapies.
Conclusions
This study provided evidence that infliximab 5 mg/kg induction and maintenance therapies are efficacious and well-tolerated in patients with moderate-to-severe active intestinal BD. (ClinicalTrials.gov identifier: NCT02505568)
7.Korean clinical practice guidelines on biologics for moderate to severe Crohn’s disease
Seong-Joon KOH ; Sung Noh HONG ; Soo-Kyung PARK ; Byong Duk YE ; Kyeong Ok KIM ; Jeong Eun SHIN ; Yong Sik YOON ; Hong Sub LEE ; Sung Hoon JUNG ; Miyoung CHOI ; Soo-Young NA ; Chang Hwan CHOI ; Joo Sung KIM ;
Intestinal Research 2023;21(1):43-60
Crohn’s disease (CD) is a relapsing and progressive condition characterized by diarrhea, abdominal pain, weight loss, and hematochezia that results in serious complications such as perforations, fistulas, and abscesses. Various medications, interventions, and surgical treatments have been used to treat CD. The Korean guidelines for CD management were distributed in 2012 and revised in 2017 by the Inflammatory Bowel Disease (IBD) Research Group of the Korean Association for the Study of Intestinal Diseases. Substantial progress in mucosal immunologic research has elucidated the pathophysiology of IBD, leading to development of biological agents for treatment of CD. The first developed biologic agent, tumor necrosis factor-α agents, were shown to be efficacious in CD, heralding a new era in management of CD. Subsequently, vedolizumab, a monoclonal antibody against integrin α4β7, and ustekinumab, a human monoclonal antibody that inhibits the common p40 subunit of interleukin-12 and interleukin-23, were both approved for clinical use and are efficacious and safe for both induction and maintenance of remission in moderate-to-severe CD patients. Moreover, a recent study showed the non-inferiority of CT-P13, an infliximab biosimilar, compared with infliximab in CD patients. The third Korean guidelines for CD management provide updated information regarding treatment of moderate-to-severe CD patients with biologic agents.
8.Clinical Features and Long-term Prognosis of Crohn’s Disease in Korea: Results from the Prospective CONNECT Study
Seung Wook HONG ; Byong Duk YE ; Jae Hee CHEON ; Ji Hyun LEE ; Ja Seol KOO ; Byung Ik JANG ; Kang-Moon LEE ; You Sun KIM ; Tae Oh KIM ; Jong Pil IM ; Geun Am SONG ; Sung-Ae JUNG ; Hyun Soo KIM ; Dong Il PARK ; Hyun-Soo KIM ; Kyu Chan HUH ; Young-Ho KIM ; Jae Myung CHA ; Geom Seog SEO ; Chang Hwan CHOI ; Hyun Joo SONG ; Gwang Ho BAIK ; Ji Won KIM ; Sung Jae SHIN ; Young Sook PARK ; Chang Kyun LEE ; Jun LEE ; Sung Hee JUNG ; Yunho JUNG ; Sung Chul PARK ; Young-Eun JOO ; Yoon Tae JEEN ; Dong Soo HAN ; Suk-Kyun YANG ; Hyo Jong KIM ; Won Ho KIM ; Joo Sung KIM
Gut and Liver 2022;16(6):907-920
Background/Aims:
The prospective Crohn’s Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn’s disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD.
Methods:
Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019).
Results:
A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35;95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection.
Conclusions
The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.
9.Clinical Outcomes of Angiography and Transcatheter Arterial Embolization for Acute Gastrointestinal Bleeding: Analyses according to Bleeding Sites and Embolization Types.
Soo Min NOH ; Ji Hoon SHIN ; Ha Il KIM ; Sun Ho LEE ; Kiju CHANG ; Eun Mi SONG ; Sung Wook HWANG ; Dong Hoon YANG ; Byong Duk YE ; Seung Jae MYUNG ; Suk Kyun YANG ; Jeong Sik BYEON
The Korean Journal of Gastroenterology 2018;71(4):219-228
BACKGROUND/AIMS: The clinical outcomes of angiography and transcatheter arterial embolization (TAE) for acute gastrointestinal bleeding (GIB) have not been completely assessed, especially according to bleeding sites. This study aimed to assess the efficacy of angiography and safety of TAE in acute GIB. METHODS: This was a retrospective study evaluating the records of 321 patients with acute GIB who underwent angiography with or without TAE. Targeted TAE was conducted in 134 patients, in whom angiography showed bleeding sources. Prophylactic TAE was performed in 29 patients when the bleeding source was not detected but a specific vessel was strongly suspected by other examinations. The rate of technical success, clinical success, and complications were analyzed. RESULTS: The detection rate of bleeding source via angiography was 50.8% (163/321), which was not different according to the bleeding sites. The detection rate was higher if the probable bleeding source had already been found by another investigation (59.7% vs. 35.8%, p<0.001). TAE sites were upper GIB in 67, mid GIB in 74, and lower GIB in 22. The technical success rate was 99.3% (133/134), and the clinical success rate was 63.0% (104/163). The prophylactic embolization group showed lower clinical success rate than the targeted embolization group (44.8% vs. 67.9%, p=0.06). The TAE-related complication rate was 12.9% (21/163). Ischemia and/or infarction was more common after TAE for mid and lower GIB than for upper GIB (15.6% vs. 3.0%, p=0.007). CONCLUSIONS: Angiography with or without TAE was an effective method for acute GIB. Targeted embolization should be performed if possible given that it has a higher clinical success rate.
Angiography*
;
Embolization, Therapeutic
;
Gastrointestinal Hemorrhage
;
Hemorrhage*
;
Humans
;
Infarction
;
Ischemia
;
Methods
;
Retrospective Studies
10.Diagnostic Yield and Clinical Impact of Video Capsule Endoscopy in Patients with Chronic Diarrhea: A Korean Multicenter CAPENTRY Study.
Hyun Joo SONG ; Jeong Seop MOON ; Seong Ran JEON ; Jin Oh KIM ; Jinsu KIM ; Dae Young CHEUNG ; Myung Gyu CHOI ; Yun Jeong LIM ; Ki Nam SHIM ; Byong Duk YE ; Jae Hee CHEON ; Cheol Hee PARK ; Hyun Soo KIM ; Ji Hyun KIM ; Dong Kyung CHANG ; Jae Hyuk DO ; Kyeong Ok KIM ; Byung Ik JANG ; Sung Jae SHIN
Gut and Liver 2017;11(2):253-260
BACKGROUND/AIMS: In some cases, chronic diarrhea is unexplained, and small bowel disorders may be one of the causes. The aim of this study was to assess the diagnostic yield and clinical impact of video capsule endoscopy (VCE) in patients with chronic diarrhea. METHODS: We retrospectively analyzed records from October 2002 to August 2013 in the VCE nationwide database registry (n=2,964). Ninety-one patients from 15 medical centers (60 males and 31 females; mean age, 47±19 years) were evaluated for VCE as a result of chronic diarrhea. RESULTS: The duration of chronic diarrhea was 8.3±14.7 months. The positive diagnostic yield of VCE was 42.9% (39/91). However, 15.4% (14/91) exhibited an inconsistent result, and 41.8% (38/91) were negative. Abnormal findings consistent with chronic diarrhea included erosions/aphthous ulcers (19.8%), ulcers (17.6%), mucosal erythema (3.3%), edema (1.1%), and luminal narrowing (1.1%). The most common diagnoses were functional diarrhea associated with irritable bowel syndrome in 37 patients (40.7%) and Crohn’s disease in 18 patients (19.8%). After VCE examination, the diagnosis was changed in 34.1% of the patients (31/91). Hematochezia (odds ratio [OR], 8.802; 95% confidence interval [CI], 2.126 to 36.441) and hypoalbuminemia (OR, 4.811; 95% CI, 1.241 to 18.655) are predictive factors of a positive diagnostic yield. CONCLUSIONS: VCE had a favorable diagnostic yield and clinical impact on the management of patients with chronic diarrhea.
Capsule Endoscopy*
;
Diagnosis
;
Diarrhea*
;
Edema
;
Erythema
;
Female
;
Gastrointestinal Hemorrhage
;
Humans
;
Hypoalbuminemia
;
Irritable Bowel Syndrome
;
Male
;
Phenobarbital
;
Retrospective Studies
;
Ulcer

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