1.Cynaropicrin Induces Reactive Oxygen Species-Dependent Paraptosis-Like Cell Death in Human Liver Cancer Cells
Min Yeong KIM ; Hee-Jae CHA ; Su Hyun HONG ; Sung-Kwon MOON ; Taeg Kyu KWON ; Young-Chae CHANG ; Gi Young KIM ; Jin Won HYUN ; A-Young NAM ; Jung-Hyun SHIM ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):470-482
Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.
2.Cynaropicrin Induces Reactive Oxygen Species-Dependent Paraptosis-Like Cell Death in Human Liver Cancer Cells
Min Yeong KIM ; Hee-Jae CHA ; Su Hyun HONG ; Sung-Kwon MOON ; Taeg Kyu KWON ; Young-Chae CHANG ; Gi Young KIM ; Jin Won HYUN ; A-Young NAM ; Jung-Hyun SHIM ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):470-482
Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.
3.Cynaropicrin Induces Reactive Oxygen Species-Dependent Paraptosis-Like Cell Death in Human Liver Cancer Cells
Min Yeong KIM ; Hee-Jae CHA ; Su Hyun HONG ; Sung-Kwon MOON ; Taeg Kyu KWON ; Young-Chae CHANG ; Gi Young KIM ; Jin Won HYUN ; A-Young NAM ; Jung-Hyun SHIM ; Yung Hyun CHOI
Biomolecules & Therapeutics 2025;33(3):470-482
Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.
4.Pancreatic metastasis from papillary thyroid cancer: a case report and literature review
Sang Hwa SONG ; Young Hoe HUR ; Chol Kyoon CHO ; Yang Seok KOH ; Eun Kyu PARK ; Hee Joon KIM ; Sang Hoon SHIN ; Sung Yeol YU ; Chae Yung OH
Korean Journal of Clinical Oncology 2023;19(1):32-37
Pancreatic metastasis from papillary thyroid cancer (PTC) is extremely rare; only 18 cases have been reported in the literature. However, several reviews have highlighted similar characteristics between metastatic and primary pancreatic tumors. The patient was a 51-year-old male with a history of total thyroidectomy, modified radical neck dissection, and radioactive iodine ablation for PTC in 2014. Nodules suspected of metastasis were found in both lungs on chest computed tomography (CT). However, after 6 months, a follow-up chest CT showed no increase in size; thus, a follow-up observation was planned. Six years after his initial diagnosis, abdominal CT and pancreas magnetic resonance imaging revealed a 4.7 cm cystic mass with a 2.5 cm enhancing mural nodule in the pancreas tail. We diagnosed the pancreatic lesion as either metastatic cancer or primary pancreas cancer. The patient underwent distal pancreato-splenectomy. After surgery, the pathological report revealed that the mass was metastatic PTC. Pancreatic metastasis from PTC indicates an advanced tumor stage and poor prognosis. However, pancreatectomy can increase the survival rate when the lesion is completely resectable. Therefore, surgical resection should be considered as a treatment for pancreatic metastasis from PTC.
5.The Prognostic Implication of Metabolic Syndrome in Patients with Heart Failure.
Hyun Ju YOON ; Youngkeun AHN ; Kye Hun KIM ; Jong Chun PARK ; Dong Ju CHOI ; Seongwoo HAN ; Eun Seok JEON ; Myung Chan CHO ; Jae Joong KIM ; Byung Su YOO ; Mi Seung SHIN ; In Whan SEONG ; Seok Min KANG ; Yung Jo KIM ; Hyung Seop KIM ; Shung Chull CHAE ; Byung Hee OH ; Myung Mook LEE ; Kyu Hyung RYU
Korean Circulation Journal 2013;43(2):87-92
BACKGROUND AND OBJECTIVES: Metabolic syndrome (MetS) increases the risk of heart failure (HF). The purpose of this study was to identify the prevalence of MetS in patients with HF and determine the syndrome's association with HF in clinical and laboratory parameters. SUBJECTS AND METHODS: A total of 3200 HF patients (67.6+/-14.5 years) enrolled in a nationwide prospective Korea HF Registry between Jan. 2005 and Oct. 2009. Patients were divided into two groups according to the presence or absence of MetS at admission: group I (presence, n=1141) and group II (absence, n=2059). RESULTS: The prevalence of MetS was 35.7% across all subjects and was higher in females (56.0%). The levels of white blood cells, platelets, creatinine, glucose, and cholesterol were significantly higher in group I than in group II. Left ventricular dimension and volume was smaller and ejection fraction was higher in group I than in group II. An ischemic cause of HF was more frequent in group I. The rates of valvular and idiopathic cause were lower in group I than in group II. The rate of mortality was lower in group I than in group II (4.9% vs. 8.3%, p<0.001). CONCLUSION: Despite the increased cardiovascular risks in MetS, MetS was found to be associated with decreased mortality in HF.
Blood Platelets
;
Cholesterol
;
Creatinine
;
Female
;
Glucose
;
Heart
;
Heart Failure
;
Humans
;
Korea
;
Leukocytes
;
Prevalence
;
Prospective Studies
6.Characteristics, Outcomes and Predictors of Long-Term Mortality for Patients Hospitalized for Acute Heart Failure: A Report From the Korean Heart Failure Registry.
Dong Ju CHOI ; Seongwoo HAN ; Eun Seok JEON ; Myeong Chan CHO ; Jae Joong KIM ; Byung Su YOO ; Mi Seung SHIN ; In Whan SEONG ; Youngkeun AHN ; Seok Min KANG ; Yung Jo KIM ; Hyung Seop KIM ; Shung Chull CHAE ; Byung Hee OH ; Myung Mook LEE ; Kyu Hyung RYU
Korean Circulation Journal 2011;41(7):363-371
BACKGROUND AND OBJECTIVES: Acute heart failure (AHF) is associated with a poor prognosis and it requires repeated hospitalizations. However, there are few studies on the characteristics, treatment and prognostic factors of AHF. The aims of this study were to describe the clinical characteristics, management and outcomes of the patients hospitalized for AHF in Korea. SUBJECTS AND METHODS: We analyzed the clinical data of 3,200 hospitalization episodes that were recorded between June 2004 and April 2009 from the Korean Heart Failure (KorHF) Registry database. The mean age was 67.6+/-14.3 years and 50% of the patients were female. RESULTS: Twenty-nine point six percent (29.6%) of the patients had a history of previous HF and 52.3% of the patients had ischemic heart disease. Left ventricular ejection fraction (LVEF) was reported for 89% of the patients. The mean LVEF was 38.5+/-15.7% and 26.1% of the patients had preserved systolic function (LVEF > or =50%), which was more prevalent in the females (34.0% vs. 18.4%, respectively, p<0.001). At discharge, 58.6% of the patients received beta-blockers (BB), 53.7% received either angiotensin converting enzyme-inhibitors or angiotensin receptor blockers (ACEi/ARB), and 58.4% received both BB and ACEi/ARB. The 1-, 2-, 3- and 4-year mortality rates were 15%, 21%, 26% and 30%, respectively. Multivariate analysis revealed that advanced age {hazard ratio: 1.023 (95% confidence interval: 1.004-1.042); p=0.020}, a previous history of heart failure {1.735 (1.150-2.618); p=0.009}, anemia {1.973 (1.271-3.063); p=0.002}, hyponatremia {1.861 (1.184-2.926); p=0.007}, a high level of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) {3.152 (1.450-6.849); p=0.004} and the use of BB at discharge {0.599 (0.360-0.997); p=0.490} were significantly associated with total death. CONCLUSION: We present here the characteristics and prognosis of an unselected population of AHF patients in Korea. The long-term mortality rate was comparable to that reported in other countries. The independent clinical risk factors included age, a previous history of heart failure, anemia, hyponatremia, a high NT-proBNP level and taking BB at discharge.
Anemia
;
Angiotensin Receptor Antagonists
;
Angiotensins
;
Female
;
Heart
;
Heart Failure
;
Hospitalization
;
Humans
;
Hyponatremia
;
Korea
;
Multivariate Analysis
;
Myocardial Ischemia
;
Natriuretic Peptide, Brain
;
Peptide Fragments
;
Prognosis
;
Registries
;
Risk Factors
;
Stroke Volume
7.A Case of Pseudoalveolar Sarcoidosis with Unilateral Pulmonary Infiltration.
Hee Kyung KIM ; Hee Jung BAN ; Su Young CHI ; Dong Ryeol CHAE ; Gye Jung CHO ; Jung Hwan LIM ; Jin Yung JU ; Yong Soo KWON ; In Jae OH ; Kyu Sik KIM ; Yu Il KIM ; Sung Chul LIM ; Young Chul KIM
Tuberculosis and Respiratory Diseases 2008;64(2):149-152
A sarcoidosis is a multisystemic granulomatous disorder that has a predilection for pulmonary involvement, and the common radiological findings for the disease are bilateral nodular or reticulonodular patterns. Pseudoalveolar sarcoidosis is a rare presentation of sarcoidosis. The radiological finding is an alveolar pattern that involves or compresses the alveoli by clustered interstitial granuloma. A 58-year-old man was admitted due to incidental findings of a unilateral consolidative lesion as seen on chest radiography. A chest computed tomography (CT) examination showed multiple bronchoalveolar consolidations that were suspicious of a malignancy. However, a percutaneous needle biopsy revealed non-caseating granuloma with an asteroid body that was compatible with sarcoidosis. After one month, the consolidative lesions improved without any treatment.
Biopsy, Needle
;
Granuloma
;
Humans
;
Incidental Findings
;
Middle Aged
;
Sarcoidosis
;
Thorax
8.Sarcoidosis Initially Presenting as a Nasal Cavity Mass Misdiagnosed as Tuberculosis.
Dong Ryeol CHAE ; Seong Uk LIM ; Gye Jung CHO ; Jung Hwan LIM ; Jin Yung JU ; Yong Soo KWON ; In Jae OH ; Kyu Sik KIM ; Yu Il KIM ; Sung Chul LIM ; Young Chul KIM
Tuberculosis and Respiratory Diseases 2008;65(2):121-124
We experienced a rare case of sinonasal sarcoidosis initially presenting as nasal cavitary mass. When the clinical course was different from that of typical tuberculosis, physician should think the possibility of sarcoidosis, and re-biopsy or retrospective review of pathological findings might be helpful.
Nasal Cavity
;
Retrospective Studies
;
Sarcoidosis
;
Tuberculosis
9.Two Cases of Fractured and Embolized Implanted Central Venous Chemoports in Lung Cancer.
Jin Yung JU ; Jae Yeong CHO ; Jung Hwan LIM ; Gye Jung CHO ; Dong Ryeol CHAE ; In Jae OH ; Kyu Sik KIM ; Yu Il KIM ; Sung Chul LIM ; Young Chul KIM ; Sang Yoon SONG ; Kook Ju NA ; Yun Hyun KIM ; Jae Kyu KIM
Tuberculosis and Respiratory Diseases 2007;63(5):449-453
Totally implanted central venous access devices for chemotherapy (chemoport) are being used increasingly in lung cancer patients. Vascular catheters are associated with various complications including infection, thrombosis as well as spontaneous fractures and embolization of the catheter, which is known as 'pinch-off syndrome'. 'Pinch-off syndrome' refers to the compression of a subclavian central venous catheter between the clavicle and first rib resulting in an intermittent or permanent obstruction, which can lead to tears, transection, or embolization. We report two cases of fractured and embolized implanted subclavian venous catheters in which the fragments were removed percutaneously. A 62-year-old man presented with back pain with a duration of a few weeks. The chest radiograph revealed complete transsection and embolization of the catheter into the right atrium. In addition, a 47-year-old woman with a chemoport had a grade 3 pinch-off sign in a chest radiograph demonstrating complete transsection and embolization of the catheter into the pulmonary artery. Both cases were managed by retrieving the embolized distal fragment percutaneously and removing the proximal section of the catheter.
Back Pain
;
Catheters
;
Central Venous Catheters
;
Clavicle
;
Drug Therapy
;
Female
;
Fractures, Spontaneous
;
Heart Atria
;
Humans
;
Lung Neoplasms*
;
Lung*
;
Middle Aged
;
Pulmonary Artery
;
Radiography, Thoracic
;
Ribs
;
Thrombosis
;
Vascular Access Devices
10.Two Cases of Iatrogenic Pneumothorax after Intra-Muscular Stimulation (IMS) Therapy.
Jun Gwang SON ; In Jae OH ; Jong Pil JEONG ; Soo Ok KIM ; Jin Yung JU ; Jung Hwan LIM ; Gye Jung CHO ; Dong Ryeol CHAE ; Kyu Sik KIM ; Yu Il KIM ; Sung Chul LIM ; Young Chul KIM
Tuberculosis and Respiratory Diseases 2007;63(5):444-448
Recently, intra-Muscular Stimulation (IMS) therapy is being increasingly used for musculoskeletal pain. This procedure is generally regarded as a safe procedure for the general public. Some cases of iatrogenic pneumothorax caused by acupuncture have been reported in the medical literature. However, a case of an IMS therapy associated pneumothorax has not reported. We experienced two cases of iatrogenic pneumothorax after IMS therapy. A 62 year-old man received IMS therapy on the right shoulder due to posterior neck pain. After IMS therapy, acute dyspnea and chest discomfort developed. The other patient was a 74 year-old woman who also received IMS therapy. This patient experienced a nonproductive cough and acute dyspnea after the treatment. As the popularity of this form of alternative medicine increases, we might expect to see more cases of iatrogenic pneumothorax. Physicians should be aware of the adverse events associated with IMS therapy.
Acupuncture
;
Aged
;
Complementary Therapies
;
Cough
;
Dyspnea
;
Female
;
Humans
;
Middle Aged
;
Musculoskeletal Pain
;
Neck Pain
;
Pneumothorax*
;
Shoulder
;
Thorax

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