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.Root and Canal Morphology of Maxillary Primary Molar using CBCT and 3D CT
Joon Hee KIM ; Hyuntae KIM ; Teo Jeon SHIN ; Hong-Keun HYUN ; Young-Jae KIM ; Jung-Wook KIM ; Ki-Taeg JANG ; Ji-Soo SONG
Journal of Korean Academy of Pediatric Dentistry 2021;48(4):437-448
The purpose of this study is to analyze morphological characteristics of maxillary primary molar’s root and root canal. 268 children aged 3 - 7 years (175 boys, 93 girls) who had CBCT (152 children) and 3D CT (116 children) taken in Seoul National University Dental Hospital from January 2006 to April 2020 were included. The number of roots and root canals were analyzed in 1002 teeth without any root resorption or periapical pathologies. Curvature, angulation, length of root and root canal, as well as cross-sectional shapes of the root canal were analyzed in 218 teeth. By using Mimics and 3-Matics software, volume, surface area, and volume ratio of root canal was analyzed in 48 teeth.
More than half of maxillary primary molars have 3 roots and 3 root canals. The degree of symmetry of root canal type was about 0.63 (Cohen’s kappa coefficient). The most frequent shape of roots and canals was linear in 1st primary molars and curved in 2nd primary molars. Angulation, length of root and root canals was the largest on palatal roots. Most teeth showed ovoid or round shapes at apex. The largest root canal volume, surface area, volume ratio was found in the palatal roots.
5.Personalized Urination Activity Recognition Based on a Recurrent Neural Network Using Smart Band.
Taeg Keun WHANGBO ; Sung Jong EUN ; Eun Young JUNG ; Dong Kyun PARK ; Su Jin KIM ; Chang Hee KIM ; Kyung Jin CHUNG ; Khae Hawn KIM
International Neurourology Journal 2018;22(Suppl 2):S91-S100
PURPOSE: Though it is very important obtaining exact data about patients’ voiding patterns for managing voiding dysfunction, actual practice is very difficult and cumbersome. In this study, data about urination time and interval measured by smart band device on patients’ wrist were collected and analyzed to resolve the clinical arguments about the efficacy of voiding diary. By developing a smart band based algorithm for recognition of complex and serial pattern of motion, this study aimed to explore the feasibility of measurement the urination time and intervals for voiding dysfunction management. METHODS: We designed a device capable of recognizing urination time and intervals based on specific postures of the patient and consistent changes in posture. These motion data were obtained by a smart band worn on the wrist. An algorithm that recognizes the repetitive and common 3-step behavior for urination (forward movement, urination, backward movement) was devised based on the movement and tilt angle data collected from a 3-axis accelerometer. The sequence of body movements during voiding has consistent temporal characteristics, so we used a recurrent neural network and long short-term memory based framework to analyze the sequential data and to recognize urination time. Real-time data were acquired from the smart band, and for data corresponding to a certain duration, the value of the signals was calculated and then compared with the set analysis model to calculate the time of urination. A comparative study was conducted between real voiding and device-detected voiding to assess the performance of the proposed recognition technology. RESULTS: The accuracy of the algorithm was calculated based on clinical guidelines established by urologists. The accuracy of this detecting device was high (up to 94.2%), proving the robustness of the proposed algorithm. CONCLUSIONS: This urination behavior recognition technology showed high accuracy and could be applied in clinical settings to characterize patients’ voiding patterns. As wearable devices are developed and generalized, algorithms detecting consistent sequential body movement patterns reflecting specific physiologic behavior might be a new methodology for studying human physiologic behavior.
Humans
;
Memory, Short-Term
;
Posture
;
Urination*
;
Wrist
6.Peripheral T-cell Lymphoma Presenting with Chylothorax.
Seong Taeg KIM ; Jaemin JO ; Jeong Rae YOO ; Miyeon KIM ; Kyoung Hee HAN ; Jung Ho KIM ; Sang Hoon HAN
Korean Journal of Medicine 2017;92(1):74-78
A 72-year-old male presented with respiratory discomfort. A simple chest X-ray and abdominal computed tomography showed pleural effusion and multiple lymph node enlargement. The pleural effusion was determined by thoracentesis to be chylothorax. An inguinal lymph node biopsy showed peripheral T-cell lymphoma. Following three cycles of cyclophospamide, hydroxyl doxorubicin, vincristine, prednisolone (CHOP) chemotherapy, a partial response was observed. Chylothorax is an extremely rare complication of T-cell lymphoma. We present a case of peripheral T-cell lymphoma presenting with chylothorax. We suggest that clinicians should consider chylothorax when examining patients with lymphoma who present with atypical pleural effusion.
Aged
;
Biopsy
;
Chylothorax*
;
Doxorubicin
;
Drug Therapy
;
Humans
;
Lymph Nodes
;
Lymphoma
;
Lymphoma, T-Cell
;
Lymphoma, T-Cell, Peripheral*
;
Male
;
Pleural Effusion
;
Prednisolone
;
Thoracentesis
;
Thorax
;
Vincristine
7.Laparoscopic total extraperitoneal hernia repair of fallopian tube indirect inguinal hernia in reproductive aged woman: a case report.
Yong Hee PARK ; Eun Jung JUNG ; Jung Mi BYUN ; Min Sung AN ; Young Nam KIM ; Kyung Bok LEE ; Moon Su SUNG ; Ki Tae KIM ; Eun Taeg KIM ; Chul Hoi JEONG ; Dae Hoon JEONG
Obstetrics & Gynecology Science 2017;60(6):608-611
An indirect inguinal hernia containing the fallopian tube alone is extremely rare in reproductive-aged women without any genital tract anomalies. Despite this rarity, early diagnosis and adequate management is important to prevent strangulation and recurrence. We present a case of an indirect inguinal hernia containing only the fallopian tube in the hernia sac, which was successfully reduced by using a laparoscopic total extraperitoneal approach and repaired with a polypropylene mesh.
Early Diagnosis
;
Fallopian Tubes*
;
Female
;
Hernia*
;
Hernia, Inguinal*
;
Herniorrhaphy*
;
Humans
;
Laparoscopy
;
Polypropylenes
;
Recurrence
8.A Case of Posterior Mediastinal Plasmacytoma Confounded by Community-Acquired Pneumonia.
Dahee HEO ; Ki Yung BOO ; Hyeyoung JWA ; Hwa Young LEE ; Jihyun KIM ; Seong Taeg KIM ; Hye Mi SEO ; Sang Hoon HAN ; Young Hee MAENG ; Jong Hoo LEE
Tuberculosis and Respiratory Diseases 2015;78(3):262-266
Plasmacytomas are extramedullary accumulations of plasma cells originating from soft tissue. Mediastinal plasmacytoma is a rare presentation. A 67-year-old man recovered after antibiotic treatment for community-acquired pneumonia. However, on convalescent chest radiography after 3 months, mass like lesion at the right lower lung field was newly detected. Follow-up chest computed tomography (CT) revealed an increase in the extent of the right posterior mediastinal mass that we had considered to be pneumonic consolidations on previous CT scans. Through percutaneous needle biopsy, we diagnosed IgG kappa type extramedullary plasmacytoma of the posterior mediastinum.
Aged
;
Biopsy, Needle
;
Diagnosis
;
Follow-Up Studies
;
Hematopoiesis, Extramedullary
;
Humans
;
Immunoglobulin G
;
Lung
;
Mediastinum
;
Plasma Cells
;
Plasmacytoma*
;
Pneumonia*
;
Radiography
;
Thorax
;
Tomography, X-Ray Computed
9.Overexpression of bone morphogenetic protein 4 in STO fibroblast feeder cells represses the proliferation of mouse embryonic stem cells in vitro.
Gu Hee KIM ; Gong Rak LEE ; Hyung Im CHOI ; Neung Hwa PARK ; Hun Taeg CHUNG ; In Seob HAN
Experimental & Molecular Medicine 2012;44(7):457-463
Embryonic stem cells (ESCs) can be propagated in vitro on feeder layers of mouse STO fibroblast cells. The STO cells secrete several cytokines that are essential for ESCs to maintain their undifferentiated state. In this study, we found significant growth inhibition of mouse ESCs (mESCs) cultured on STO cells infected with adenovirus containing a dominant-negative mutant form of IkappaB (rAd-dnIkappaB). This blockage of the NF-kappaB signal pathway in STO cells led to a significant decrease in [3H]thymidine incorporation and colony formation of mESCs. Expression profile of cytokines secreted from the STO cells revealed an increase in the bone morphogenetic protein4 (BMP4) transcript level in the STO cells infected with adenoviral vector encoding dominant negative IkappaB (rAd-dnIkappaB). These results suggested that the NF-kappaB signaling pathway represses expression of BMP4 in STO feeder cells. Conditioned medium from the rAd-dnIkappaB-infected STO cells also significantly reduced the colony size of mESCs. Addition of BMP4 prevented colony formation of mESCs cultured in the conditioned medium. Our finding suggested that an excess of BMP4 in the conditioned medium also inhibits proliferation of mESCs.
Animals
;
*Bone Morphogenetic Protein 4/genetics/metabolism
;
Cell Differentiation/genetics
;
Cell Proliferation
;
Culture Media, Conditioned
;
*Embryonic Stem Cells/cytology/metabolism
;
*Feeder Cells/cytology/metabolism
;
*Fibroblasts/cytology/metabolism
;
Gene Expression Regulation/genetics
;
*I-kappa B Proteins/genetics/metabolism
;
Mice
;
Mutation
;
NF-kappa B/genetics/metabolism
;
Signal Transduction
10.Paxilline enhances TRAIL-mediated apoptosis of glioma cells via modulation of c-FLIP, survivin and DR5.
You Jung KANG ; In Young KIM ; Eun Hee KIM ; Mi Jin YOON ; Seung U KIM ; Taeg Kyu KWON ; Kyeong Sook CHOI
Experimental & Molecular Medicine 2011;43(1):24-34
Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) induces apoptosis selectively in cancer cells while sparing normal cells. However, many cancer cells are resistant to TRAIL-induced cell death. Here, we report that paxilline, an indole alkaloid from Penicillium paxilli, can sensitize various glioma cells to TRAIL-mediated apoptosis. While treatment with TRAIL alone caused partial processing of caspase-3 to its p20 intermediate in TRAIL-resistant glioma cell lines, co-treatment with TRAIL and subtoxic doses of paxilline caused complete processing of caspase-3 into its active subunits. Paxilline treatment markedly upregulated DR5, a receptor of TRAIL, through a CHOP/GADD153-mediated process. In addition, paxilline treatment markedly downregulated the protein levels of the short form of the cellular FLICE-inhibitory protein (c-FLIPS) and the caspase inhibitor, survivin, through proteasome-mediated degradation. Taken together, these results show that paxilline effectively sensitizes glioma cells to TRAIL-mediated apoptosis by modulating multiple components of the death receptor-mediated apoptotic pathway. Interestingly, paxilline/TRAIL co-treatment did not induce apoptosis in normal astrocytes, nor did it affect the protein levels of CHOP, DR5 or survivin in these cells. Thus, combined treatment regimens involving paxilline and TRAIL may offer an attractive strategy for safely treating resistant gliomas.
Antineoplastic Agents/*pharmacology
;
Apoptosis/*drug effects
;
Astrocytes/metabolism
;
CASP8 and FADD-Like Apoptosis Regulating Protein/genetics/*metabolism
;
Caspase 3/metabolism
;
Cell Line, Tumor
;
Drug Discovery
;
Flow Cytometry
;
Glioma/*metabolism/pathology
;
Humans
;
Indoles/*pharmacology
;
Inhibitor of Apoptosis Proteins/metabolism
;
RNA, Small Interfering
;
Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics/metabolism
;
Reverse Transcriptase Polymerase Chain Reaction
;
TNF-Related Apoptosis-Inducing Ligand/metabolism/*pharmacology
;
Transcription Factor CHOP/analysis

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