1.Gaps and Similarities in Research Use LOINC Codes Utilized in Korean University Hospitals: Towards Semantic Interoperability for Patient Care
Kuenyoul PARK ; Min-Sun KIM ; YeJin OH ; John Hoon RIM ; Shinae YU ; Hyejin RYU ; Eun-Jung CHO ; Kyunghoon LEE ; Ha Nui KIM ; Inha CHUN ; AeKyung KWON ; Sollip KIM ; Jae-Woo CHUNG ; Hyojin CHAE ; Ji Seon OH ; Hyung-Doo PARK ; Mira KANG ; Yeo-Min YUN ; Jong-Baeck LIM ; Young Kyung LEE ; Sail CHUN
Journal of Korean Medical Science 2025;40(1):e4-
Background:
The accuracy of Logical Observation Identifiers Names and Codes (LOINC) mappings is reportedly low, and the LOINC codes used for research purposes in Korea have not been validated for accuracy or usability. Our study aimed to evaluate the discrepancies and similarities in interoperability using existing LOINC mappings in actual patient care settings.
Methods:
We collected data on local test codes and their corresponding LOINC mappings from seven university hospitals. Our analysis focused on laboratory tests that are frequently requested, excluding clinical microbiology and molecular tests. Codes from nationwide proficiency tests served as intermediary benchmarks for comparison. A research team, comprising clinical pathologists and terminology experts, utilized the LOINC manual to reach a consensus on determining the most suitable LOINC codes.
Results:
A total of 235 LOINC codes were designated as optimal codes for 162 frequent tests.Among these, 51 test items, including 34 urine tests, required multiple optimal LOINC codes, primarily due to unnoted properties such as whether the test was quantitative or qualitative, or differences in measurement units. We analyzed 962 LOINC codes linked to 162 tests across seven institutions, discovering that 792 (82.3%) of these codes were consistent. Inconsistencies were most common in the analyte component (38 inconsistencies, 33.3%), followed by the method (33 inconsistencies, 28.9%), and properties (13 inconsistencies, 11.4%).
Conclusion
This study reveals a significant inconsistency rate of over 15% in LOINC mappings utilized for research purposes in university hospitals, underlining the necessity for expert verification to enhance interoperability in real patient care.
2.Nutrition Status and Comorbidities Are Important Factors Associated With Mortality During Anti-Tuberculosis Treatment
Oh Beom KWON ; Hyung Woo KIM ; Ju Sang KIM ; Eung Gu LEE ; Yeonhee PARK ; Sung Soo JUNG ; Jin Woo KIM ; Jee Youn OH ; Sang Haak LEE ; Seunghoon KIM ; Sun-Hyung KIM ; Jiwon LYU ; Yousang KO ; Sun Jung KWON ; Ganghee CHAE ; Jinsoo MIN
Journal of Korean Medical Science 2025;40(17):e73-
Background:
The increasing incidence and mortality rates of tuberculosis among older individuals who suffer from multiple morbidities and are vulnerable to malnutrition are major obstacles to efforts to eradicate tuberculosis in the Republic of Korea. Herein, we identified the factors associated with mortality during anti-tuberculosis treatment in patients with pulmonary tuberculosis.
Methods:
We conducted a case-control study and extracted data from the database of a multi-center prospective observational cohort study in Korea. Among the participants with rifampicin-susceptible pulmonary tuberculosis, the survival group was defined as those who successfully completed treatment within one year, whereas the mortality group was defined as those who died during treatment. Univariable and multivariable logistic regression analyses were performed to identify factors associated with TB mortality.
Results:
Among 1,119 participants with pulmonary TB registered between 2019 and 2021, 799 and 59 were grouped in the survival and mortality groups, respectively. Age, positive smear results, alarming symptoms, nutrition risk score, Charlson comorbidity index score, and initial standard treatment regimen were significant based on univariable analysis and were selected for the multivariable logistic regression model. Nutrition risk score (adjusted odds ratio, 2.44; 95% confidence interval, 1.72–3.48) and Charlson comorbidity index score (adjusted odds ratio, 1.62; 95% confidence interval, 1.35–1.94) remained statistically significant in the multivariate analysis.
Conclusion
Nutritional status and comorbidities at baseline were identified as important factors associated with mortality in patients with pulmonary tuberculosis.
3.Assessing and Charting the Future Path : Addressing the Decline of Brain Tumor Specialists in Korea - Insights from the Korean Brain Tumor Society (KBTS) Future Strategy Committee of 2023
Joonho BYUN ; Kyeong-O GO ; Kyung-Min KIM ; Dong-Won SHIN ; Jihwan YOO ; Yeo Song KIM ; Sae Min KWON ; Young Zoon KIM ; Seon-Hwan KIM
Journal of Korean Neurosurgical Society 2025;68(1):97-104
Objective:
: Although Republic of Korea is an advanced country in medical technology with a successful treatment rate for serious diseases, such as cancer, and has improved technology for highly difficult surgery, many excellent medical doctors and physicians are struggling due to the recent unreasonable medical environment. Specialization in brain tumor surgery also faces challenges in Republic of Korea, including low financial incentives, legal threats, and limited career prospects. In response, the Korean Brain Tumor Society (KBTS) formed the Future Strategy Committee to assess these obstacles and propose solutions.
Methods:
: A survey was conducted among the KBTS members to understand their perceptions and concerns across different career stages.
Results:
: The findings revealed a decline in interest among chief residents in brain tumor surgery, owing to limited job opportunities and income prospects. Neurosurgical fellows expressed neutral satisfaction but highlighted challenges, such as low patient numbers and income. Faculty members with varying levels of experience echoed similar concerns, emphasizing the need for improved financial incentives and job stability. Despite these challenges, the respondents expressed dedication to the field and suggested strategies for improvement.
Conclusion
: The KBTS outlines a vision that focuses on practical excellence, comprehensive research, professional education, responsibilities, and member satisfaction. Addressing these challenges requires collaborative efforts among healthcare institutions, professional societies, and policymakers to support brain tumor specialists and enhance patient care.
4.Strategic Dual Approach for the Management of a Symptomatic Giant Partially Thrombosed Aneurysm at the Basilar Tip - Integrating Intrasaccular Flow Diversion and Endovascular Flow Reversal
Se Yun KIM ; Jong Min LEE ; Soon Chan KWON
Journal of Korean Neurosurgical Society 2025;68(2):234-240
Managing giant partially thrombosed intracranial aneurysms presents significant challenges due to their unfavorable natural history and the lack of standardized treatment approaches. Conventional treatments, whether open surgical or endovascular, often struggle to manage these aneurysms effectively, resulting in high recurrence rates or significant morbidity. The patient was a 62-year-old male with a symptomatic giant partially thrombosed aneurysm at the tip of the basilar artery, presenting with left-sided hemiparesis and dysarthria. Diagnostic imaging revealed a giant aneurysm with a wide-necked, canalized portion. A two-stage endovascular treatment was conducted, involving a balloon occlusion test and intraoperative monitoring for maximum patient safety. The treatment utilized stent-assisted Woven EndoBridge (WEB) embolization and serial bilateral vertebral artery trapping. The procedure successfully isolated the aneurysm and postoperative imaging confirmed the absence of recanalization, preserving the intact posterior circulation. The patient showed stable recovery and no neurological deficits during the 12-month follow-up period. This technical note demonstrates the feasibility and efficacy of strategically integrating intrasaccular flow diversion using a WEB device and flow reversal through bilateral vertebral artery trapping for treating giant partially thrombosed aneurysms.
5.Single port–assisted diverting ileostomy formation for anastomotic leakage after low anterior resection
Kyong-Min KANG ; Heung-Kwon OH ; Hong-min AHN ; Hye-Rim SHIN ; Min-Hyeong JO ; Mi-Jeong CHOI ; Duck-Woo KIM ; Sung-Bum KANG
Journal of Minimally Invasive Surgery 2025;28(1):47-49
Stoma formation for fecal diversion is a common procedure in patients with various complicated conditions after colorectal surgery, such as anastomotic leakage. The singleincision laparoscopic approach for stoma creation offers several advantages, including a reduction in surgical wounds and related complications as well as optimal visualization of the surgical field. This video demonstrates a single-port–assisted diverting ileostomy in a 61-yearold man with anastomotic leakage following low anterior resection for advanced rectal cancer.
6.Recanalization Outcomes and Procedural Complications in Patients With Acute Ischemic Stroke and COVID-19 Receiving Endovascular Treatment
João Pedro MARTO ; Davide STRAMBO ; George NTAIOS ; Thanh N NGUYEN ; Pawel WRONA ; Simon ESCALARD ; Simona MARCHESELLI ; Ossama Yassin MANSOUR ; Blanca FUENTES ; Malgorzata DOROBEK ; Marta NOWAKOWSKA-KOTAS ; Elena Oana TERECOASA ; Jonathan M. COUTINHO ; Mariana CARVALHO-DIAS ; Patricia CALLEJA ; João SARGENTO-FREITAS ; Ana PAIVA-NUNES ; Martin ŠRÁMEK ; Priyank KHANDELWAL ; Torcato MEIRA ; Mohamad ABDALKADER ; Pascal JABBOUR ; Martin KOVÁŘ ; Oscar AYO-MARTIN ; Patrik MICHEL ; Roman HERZIG ; Anna CZŁONKOWKSA ; Jelle DEMEESTERE ; Raul G. NOGUEIRA ; Alexander SALERNO ; Susanne WEGENER ; Philipp BAUMGARTNER ; Carlo W. CEREDA ; Giovanni BIANCO ; Morin BEYELER ; Marcel ARNOLD ; Emmanuel CARRERA ; Paolo MACHI ; Valerian ALTERSBERGER ; Leo BONATI ; Henrik GENSICKE ; Manuel BOLOGNESE ; Nils PETERS ; Stephan WETZEL ; Marta MAGRIÇO ; João NUNO RAMOS ; Rita MACHADO ; Carolina MAIA ; Egídio MACHADO ; Patrícia FERREIRA ; Teresa PINHO-E-MELO ; André PAULA ; Manuel Alberto CORREIA ; Pedro CASTRO ; Elsa AZEVEDO ; Luís ALBUQUERQUE ; José NUNO-ALVES ; Joana FERREIRA-PINTO ; Torcato MEIRA ; Liliana PEREIRA ; Miguel RODRIGUES ; André ARAÚJO ; Marta RODRIGUES ; Mariana ROCHA ; Ângelo PEREIRA-FONSECA ; Luís RIBEIRO ; Ricardo VARELA ; Sofia MALHEIRO ; Manuel CAPPELLARI ; Cecilia ZIVELONGHI ; Giulia SAJEVA ; Andrea ZINI ; Gentile MAURO ; Forlivesi STEFANO ; Ludovica MIGLIACCIO ; Maria SESSA ; Sara La GIOIA ; Alessandro PEZZINI ; Davide SANGALLI ; Marialuisa ZEDDE ; Rosario PASCARELLA ; Carlo FERRARESE ; Simone BERETTA ; Susanna DIAMANTI ; Ghil SCHWARZ ; Giovanni FRISULLO ; Pierre SENERS ; Candice SABBEN ; Michel PIOTIN ; Benjamin MAIER ; Guillaume CHARBONNIER ; Fabrice VUILLIER ; Loic LEGRIS ; Pauline CUISENIER ; Francesca R. VODRET ; Gaultier MARNAT ; Jean-Sebastien LIEGEY ; Igor SIBON ; Fabian FLOTTMANN ; Gabriel BROOCKS ; Nils-Ole GLOYER ; Ferdinand O. BOHMANN ; Jan Hendrik SCHAEFER ; Christian H. NOLTE ; Heinrich AUDEBERT ; Eberhard SIEBERT ; Marek SYKORA ; Wilfried LANG ; Julia FERRARI ; Lukas MAYER-SUESS ; Michael KNOFLACH ; Elke-Ruth GIZEWSKI ; Jeffrey STOLP ; Lotte J. STOLZE ; Paul J. NEDERKOORN ; Ido VAN-DEN-WIJNGAARD ; Joke DE MERIS ; Robin LEMMEN ; Sylvie DE RAEDT ; Fenne VANDERVORST ; Matthieu Pierre RUTGERS ; Antoine GUILMOT ; Anne DUSART ; Flavio BELLANTE ; Fernando OSTOS ; Guillermo GONZALEZ-ORTEGA ; Paloma MARTÍN-JIMÉNEZ ; Sebastian GARCÍA-MADRONA ; Antonio CRUZ-CULEBRAS ; Rocio VERA ; Maria-Consuelo MATUTE ; María ALONSO-DE-LECIÑANA ; Ricardo RIGUAL ; Exuperio DÍEZ-TEJEDOR ; Soledad PÉREZ-SÁNCHEZ ; Joan MONTANER ; Fernando DÍAZ-OTERO ; Natalia PEREZ-DE-LA-OSSA ; Belén FLORES-PINA ; Lucia MUÑOZ-NARBONA ; Angel CHAMORRO ; Alejandro RODRÍGUEZ-VÁZQUEZ ; Arturo RENÚ ; Francisco HERNANDEZ-FERNANDEZ ; Tomas SEGURA ; Herbert TEJADA-MEZA ; Daniel SAGARRA-MUR ; Marta SERRANO-PONZ ; Thant HLAING ; Isaiah SEE ; Robert SIMISTER ; David J. WERRING ; Espen Saxhaug KRISTOFFERSEN ; Annika NORDANSTIG ; Katarina JOOD ; Alexandros RENTZOS ; Libor ŠIMU˚NE ; Dagmar KRAJÍČKOVÁ ; Antonín KRAJINA ; Robert MIKULÍK ; Martina CVIKOVÁ ; Jan VINKLÁREK ; David ŠKOLOUDÍK ; Martin ROUBEC ; Eva HURTIKOVA ; Rostislav HRUBÝ ; Svatopluk OSTRY ; Ondrej SKODA ; Marek PERNICKA ; Lubomír KOČÍ ; Zuzana EICHLOVÁ ; Martin JÍRA ; Michal PANSKÝ ; Pavel MENCL ; Hana PALOUŠKOVÁ ; Aleš TOMEK ; Petr JANSKÝ ; Anna OLŠEROVÁ ; Roman HAVLÍČEK ; Petr MALÝ ; Lukáš TRAKAL ; Jan FIKSA ; Matěj SLOVÁK ; Michał KARLIŃSK ; Maciej NOWAK ; Halina SIENKIEWICZ-JAROSZ ; Anna BOCHYNSKA ; Tomasz HOMA ; Katarzyna SAWCZYNSKA ; Agnieszka SLOWIK ; Ewa WLODARCZYK ; Marcin WIĄCEK ; Izabella TOMASZEWSKA-LAMPART ; Bartosz SIECZKOWSKI ; Halina BARTOSIK-PSUJEK ; Marta BILIK ; Anna BANDZAREWICZ ; Justyna ZIELIŃSKA-TUREK ; Krystian OBARA ; Paweł URBANOWSKI ; Sławomir BUDREWICZ ; Maciej GUZIŃSKI ; Milena ŚWITOŃSKA ; Iwona RUTKOWSKA ; Paulina SOBIESZAK-SKURA ; Beata ŁABUZ-ROSZAK ; Aleksander DĘBIEC ; Jacek STASZEWSKI ; Adam STĘPIEŃ ; Jacek ZWIERNIK ; Grzegorz WASILEWSKI ; Cristina TIU ; Razvan-Alexandru RADU ; Anca NEGRILA ; Bogdan DOROBAT ; Cristina PANEA ; Vlad TIU ; Simona PETRESCU ; Atilla ÖZCAN-ÖZDEMIR ; Mostafa MAHMOUD ; Hussam EL-SAMAHY ; Hazem ABDELKHALEK ; Jasem AL-HASHEL ; Ismail IBRAHIM ISMAIL ; Athari SALMEEN ; Abdoreza GHOREISHI ; Sergiu SABETAY ; Hana GROSS ; Piers KLEIN ; Kareem EL NAAMANI ; Stavropoula TJOUMAKARIS ; Rawad ABBAS ; Ghada-A MOHAMED ; Alex CHEBL ; Jiangyong MIN ; Majesta HOVINGH ; Jenney-P TSAI ; Muhib-A KHAN ; Krishna NALLEBALLE ; Sanjeeva ONTEDDU ; Hesham-E MASOUD ; Mina MICHAEL ; Navreet KAUR ; Laith MAALI ; Michael ABRAHAM ; Ivo BACH ; Melody ONG ; Denis BABICI ; Ayaz-M. KHAWAJA ; Maryam HAKEMI ; Kumar RAJAMANI ; Vanessa CANO-NIGENDA ; Antonio ARAUZ ; Pablo AMAYA ; Natalia LLANOS ; Akemi ARANGO ; Miguel A. VENCES ; José-Domingo BARRIENTOS ; Rayllene CAETANO ; Rodrigo TARGA ; Sergio SCOLLO ; Patrick YALUNG ; Shashank NAGENDRA ; Abhijit GAIKWAD ; Kwon-Duk SEO ;
Journal of Stroke 2025;27(1):128-132
7.Low-Density Lipoprotein Cholesterol Level, the Lower the Better? Analysis of Korean Patients in the Treat Stroke to Target Trial
Hanim KWON ; Jae-Chan RYU ; Jae-Kwan CHA ; Sang Min SUNG ; Tae-Jin SONG ; Kyung Bok LEE ; Eung-Gyu KIM ; Yong-Won KIM ; Ji Hoe HEO ; Man Seok PARK ; Kyusik KANG ; Byung-Chul LEE ; Keun-Sik HONG ; Oh Young BANG ; Jei KIM ; Jong S. KIM
Journal of Stroke 2025;27(2):228-236
Background:
and Purpose The Treat Stroke to Target (TST) was a randomized clinical trial involving French and Korean patients demonstrating that a lower low-density lipoprotein cholesterol (LDL-C, <70 mg/dL) target group (LT) experienced fewer cerebro-cardiovascular events than a higher target (90–110 mg/dL) group (HT). However, whether these results can be applied to Asian patients with different ischemic stroke subtypes remains unclear.
Methods:
Patients from 14 South Korean centers were analyzed separately. Patients with ischemic stroke or transient ischemic attack with evidence of atherosclerosis were randomized into LT and HT groups. The primary endpoint was a composite of ischemic stroke, myocardial infarction, coronary or cerebral revascularization, and cardiovascular death.
Results:
Among 712 enrolled patients, the mean LDL-C level was 71.0 mg/dL in 357 LT patients and 86.1 mg/dL in 355 HT patients. The primary endpoint occurred in 24 (6.7%) of LT and in 31 (8.7%) of HT group patients (adjusted hazard ratio [HR]=0.78; 95% confidence interval [CI]=0.45–1.33, P=0.353). Cardiovascular events alone occurred significantly less frequently in the LT than in the HT group (HR 0.26, 95% CI 0.09–0.80, P=0.019), whereas there were no significant differences in ischemic stroke events (HR 1.12, 95% CI 0.60–2.10, P=0.712). The benefit of LT was less apparent in patients with small vessel disease and intracranial atherosclerosis than in those with extracranial atherosclerosis.
Conclusion
In contrast to the French TST, the outcomes in Korean patients were neutral. Although LT was more effective in preventing cardiovascular diseases, it was not so in stroke prevention, probably attributed to the differences in stroke subtypes. Further studies are needed to elucidate the efficacy of statins and appropriate LDL-C targets in Asian patients with stroke.
8.Deep Learning Technology for Classification of Thyroid Nodules Using Multi-View Ultrasound Images: Potential Benefits and Challenges in Clinical Application
Jinyoung KIM ; Min-Hee KIM ; Dong-Jun LIM ; Hankyeol LEE ; Jae Jun LEE ; Hyuk-Sang KWON ; Mee Kyoung KIM ; Ki-Ho SONG ; Tae-Jung KIM ; So Lyung JUNG ; Yong Oh LEE ; Ki-Hyun BAEK
Endocrinology and Metabolism 2025;40(2):216-224
Background:
This study aimed to evaluate the applicability of deep learning technology to thyroid ultrasound images for classification of thyroid nodules.
Methods:
This retrospective analysis included ultrasound images of patients with thyroid nodules investigated by fine-needle aspiration at the thyroid clinic of a single center from April 2010 to September 2012. Thyroid nodules with cytopathologic results of Bethesda category V (suspicious for malignancy) or VI (malignant) were defined as thyroid cancer. Multiple deep learning algorithms based on convolutional neural networks (CNNs) —ResNet, DenseNet, and EfficientNet—were utilized, and Siamese neural networks facilitated multi-view analysis of paired transverse and longitudinal ultrasound images.
Results:
Among 1,048 analyzed thyroid nodules from 943 patients, 306 (29%) were identified as thyroid cancer. In a subgroup analysis of transverse and longitudinal images, longitudinal images showed superior prediction ability. Multi-view modeling, based on paired transverse and longitudinal images, significantly improved the model performance; with an accuracy of 0.82 (95% confidence intervals [CI], 0.80 to 0.86) with ResNet50, 0.83 (95% CI, 0.83 to 0.88) with DenseNet201, and 0.81 (95% CI, 0.79 to 0.84) with EfficientNetv2_ s. Training with high-resolution images obtained using the latest equipment tended to improve model performance in association with increased sensitivity.
Conclusion
CNN algorithms applied to ultrasound images demonstrated substantial accuracy in thyroid nodule classification, indicating their potential as valuable tools for diagnosing thyroid cancer. However, in real-world clinical settings, it is important to aware that model performance may vary depending on the quality of images acquired by different physicians and imaging devices.
9.Quercetin-3-Methyl Ether Induces Early Apoptosis to Overcome HRV1B Immune Evasion, Suppress Viral Replication, and Mitigate Inflammatory Pathogenesis
Jae-Hyoung SONG ; Seo-Hyeon MUN ; Sunil MISHRA ; Seong-Ryeol KIM ; Heejung YANG ; Sun Shim CHOI ; Min-Jung KIM ; Dong-Yeop KIM ; Sungchan CHO ; Youngwook HAM ; Hwa-Jung CHOI ; Won-Jin BAEK ; Yong Soo KWON ; Jae-Hoon CHANG ; Hyun-Jeong KO
Biomolecules & Therapeutics 2025;33(2):388-398
Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.
10.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.

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