1.Gene Expression Alteration by Non-thermal Plasma-Activated Media Treatment in Radioresistant Head and Neck Squamous Cell Carcinoma
Sicong ZHENG ; Yudan PIAO ; Seung-Nam JUNG ; Chan OH ; Mi Ae LIM ; QuocKhanh NGUYEN ; Shan SHEN ; Se-Hee PARK ; Shengzhe CUI ; Shuyu PIAO ; Young Il KIM ; Ji Won KIM ; Ho-Ryun WON ; Jae Won CHANG ; Yujuan SHAN ; Lihua LIU ; Bon Seok KOO
Clinical and Experimental Otorhinolaryngology 2025;18(1):73-87
Objectives:
. Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes.
Methods:
. After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC.
Results:
. NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways.
Conclusion
. NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.
2.Gene Expression Alteration by Non-thermal Plasma-Activated Media Treatment in Radioresistant Head and Neck Squamous Cell Carcinoma
Sicong ZHENG ; Yudan PIAO ; Seung-Nam JUNG ; Chan OH ; Mi Ae LIM ; QuocKhanh NGUYEN ; Shan SHEN ; Se-Hee PARK ; Shengzhe CUI ; Shuyu PIAO ; Young Il KIM ; Ji Won KIM ; Ho-Ryun WON ; Jae Won CHANG ; Yujuan SHAN ; Lihua LIU ; Bon Seok KOO
Clinical and Experimental Otorhinolaryngology 2025;18(1):73-87
Objectives:
. Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes.
Methods:
. After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC.
Results:
. NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways.
Conclusion
. NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.
3.Gene Expression Alteration by Non-thermal Plasma-Activated Media Treatment in Radioresistant Head and Neck Squamous Cell Carcinoma
Sicong ZHENG ; Yudan PIAO ; Seung-Nam JUNG ; Chan OH ; Mi Ae LIM ; QuocKhanh NGUYEN ; Shan SHEN ; Se-Hee PARK ; Shengzhe CUI ; Shuyu PIAO ; Young Il KIM ; Ji Won KIM ; Ho-Ryun WON ; Jae Won CHANG ; Yujuan SHAN ; Lihua LIU ; Bon Seok KOO
Clinical and Experimental Otorhinolaryngology 2025;18(1):73-87
Objectives:
. Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes.
Methods:
. After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC.
Results:
. NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways.
Conclusion
. NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.
4.Carrier Frequency and Incidence of MUTYH-Associated Polyposis Based on Database Analysis in East Asians and Koreans
Jong Eun PARK ; Taeheon LEE ; Eun Hye CHO ; Mi-Ae JANG ; Dongju WON ; Boyoung PARK ; Chang-Seok KI ; Sun-Young KONG
Annals of Laboratory Medicine 2025;45(1):77-84
Background:
MUTYH-associated polyposis is an autosomal recessive disorder associated with an increased lifetime risk of colorectal cancer and a moderately increased risk of ovarian, bladder, breast, and endometrial cancers. We analyzed the carrier frequency and estimated the incidence of MUTYH-associated polyposis in East Asian and Korean populations, for which limited data were previously available.
Methods:
We examined 125,748 exomes from the gnomAD database, including 9,197 East Asians, and additional data from 5,305 individuals in the Korean Variant Archive and 1,722 in the Korean Reference Genome Database. All MUTYH variants were interpreted according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines and the Sequence Variant Interpretation guidelines from ClinGen.
Results:
The global carrier frequency of MUTYH-associated polyposis was 1.29%, with Europeans (non-Finnish) having the highest frequency of 1.86% and Ashkenazi Jews the lowest at 0.06%. East Asians and Koreans had a carrier frequency of 0.35% and 0.37% and an estimated incidence of 1 in 330,409 and 1 in 293,304 in Koreans, respectively, which were substantially lower than the global average of 1 in 24,160 and the European (nonFinnish) incidence of 1 in 11,520.
Conclusions
This was the first study to investigate the frequency of carriers of MUTYH-associated polyposis in East Asians, including specific subgroups, utilizing gnomAD and a Korean genome database. Our data provide valuable reference information for future investigations of MUTYH-associated polyposis to understand the genetic diversity and specific variants associated with this condition in East Asian populations.
5.Survey on Treatment-Seeking Patterns in Patients With Allergic Rhinitis
Gwanghui RYU ; Do Hyun KIM ; Chang Yeong JEONG ; Sang Min LEE ; Il Hwan LEE ; Soo Whan KIM ; Hyeon-Jong YANG ; Mi-Ae KIM ; Dong-Kyu KIM ;
Journal of Rhinology 2024;31(3):138-144
Background and Objectives:
The medications preferred by patients for allergic rhinitis and their usage remain unclear. This study investigated treatment-seeking behaviors in patients with allergic rhinitis, including medical treatments, environmental controls, and surgical treatments.
Methods:
In this study, a cross-sectional survey was conducted by internal medicine, pediatric, or otorhinolaryngology physicians at university hospitals from January 2022 to April 2022. A questionnaire was administered to patients with confirmed allergic rhinitis to collect information regarding medical treatments (prescription and over-the-counter medication use patterns, comorbid asthma, and allergen-specific immunotherapy), environmental controls (usage of air purifiers and pet avoidance), and experiences with surgical treatments.
Results:
We included 51 patients with allergic rhinitis with a mean age of 31.6±16.0 years. Among them, 47 (92.2%) and 6 (11.8%) patients had pollen allergies and asthma, respectively. Furthermore, 41 (80.4%) patients took prescribed medicines, while 39 (76.5%) patients only used the medication when experiencing symptoms. Thirty patients (58.8%) reported concurrent use of intranasal sprays and oral medications. Thirty-three patients (64.7%) reported awareness of immunotherapy, and there were no preferential differences between subcutaneous (52%) and sublingual immunotherapy (48%). Of the 36 patients (70.6%) who reported using an air purifier, 38.9% considered it helpful in preventing allergic rhinitis symptoms. Fourteen patients (27.5%) currently or previously had a companion animal, with half experiencing worsening of symptoms. Twelve patients had received surgical treatment and reported high satisfaction levels (41.6%, very satisfied; 41.6%, satisfied).
Conclusion
Patients with allergic rhinitis showed similar preferences for oral and spray medications. They also showed satisfaction with surgical treatments and an interest in the environmental management of allergic rhinitis.
6.Survey on Treatment-Seeking Patterns in Patients With Allergic Rhinitis
Gwanghui RYU ; Do Hyun KIM ; Chang Yeong JEONG ; Sang Min LEE ; Il Hwan LEE ; Soo Whan KIM ; Hyeon-Jong YANG ; Mi-Ae KIM ; Dong-Kyu KIM ;
Journal of Rhinology 2024;31(3):138-144
Background and Objectives:
The medications preferred by patients for allergic rhinitis and their usage remain unclear. This study investigated treatment-seeking behaviors in patients with allergic rhinitis, including medical treatments, environmental controls, and surgical treatments.
Methods:
In this study, a cross-sectional survey was conducted by internal medicine, pediatric, or otorhinolaryngology physicians at university hospitals from January 2022 to April 2022. A questionnaire was administered to patients with confirmed allergic rhinitis to collect information regarding medical treatments (prescription and over-the-counter medication use patterns, comorbid asthma, and allergen-specific immunotherapy), environmental controls (usage of air purifiers and pet avoidance), and experiences with surgical treatments.
Results:
We included 51 patients with allergic rhinitis with a mean age of 31.6±16.0 years. Among them, 47 (92.2%) and 6 (11.8%) patients had pollen allergies and asthma, respectively. Furthermore, 41 (80.4%) patients took prescribed medicines, while 39 (76.5%) patients only used the medication when experiencing symptoms. Thirty patients (58.8%) reported concurrent use of intranasal sprays and oral medications. Thirty-three patients (64.7%) reported awareness of immunotherapy, and there were no preferential differences between subcutaneous (52%) and sublingual immunotherapy (48%). Of the 36 patients (70.6%) who reported using an air purifier, 38.9% considered it helpful in preventing allergic rhinitis symptoms. Fourteen patients (27.5%) currently or previously had a companion animal, with half experiencing worsening of symptoms. Twelve patients had received surgical treatment and reported high satisfaction levels (41.6%, very satisfied; 41.6%, satisfied).
Conclusion
Patients with allergic rhinitis showed similar preferences for oral and spray medications. They also showed satisfaction with surgical treatments and an interest in the environmental management of allergic rhinitis.
7.Survey on Treatment-Seeking Patterns in Patients With Allergic Rhinitis
Gwanghui RYU ; Do Hyun KIM ; Chang Yeong JEONG ; Sang Min LEE ; Il Hwan LEE ; Soo Whan KIM ; Hyeon-Jong YANG ; Mi-Ae KIM ; Dong-Kyu KIM ;
Journal of Rhinology 2024;31(3):138-144
Background and Objectives:
The medications preferred by patients for allergic rhinitis and their usage remain unclear. This study investigated treatment-seeking behaviors in patients with allergic rhinitis, including medical treatments, environmental controls, and surgical treatments.
Methods:
In this study, a cross-sectional survey was conducted by internal medicine, pediatric, or otorhinolaryngology physicians at university hospitals from January 2022 to April 2022. A questionnaire was administered to patients with confirmed allergic rhinitis to collect information regarding medical treatments (prescription and over-the-counter medication use patterns, comorbid asthma, and allergen-specific immunotherapy), environmental controls (usage of air purifiers and pet avoidance), and experiences with surgical treatments.
Results:
We included 51 patients with allergic rhinitis with a mean age of 31.6±16.0 years. Among them, 47 (92.2%) and 6 (11.8%) patients had pollen allergies and asthma, respectively. Furthermore, 41 (80.4%) patients took prescribed medicines, while 39 (76.5%) patients only used the medication when experiencing symptoms. Thirty patients (58.8%) reported concurrent use of intranasal sprays and oral medications. Thirty-three patients (64.7%) reported awareness of immunotherapy, and there were no preferential differences between subcutaneous (52%) and sublingual immunotherapy (48%). Of the 36 patients (70.6%) who reported using an air purifier, 38.9% considered it helpful in preventing allergic rhinitis symptoms. Fourteen patients (27.5%) currently or previously had a companion animal, with half experiencing worsening of symptoms. Twelve patients had received surgical treatment and reported high satisfaction levels (41.6%, very satisfied; 41.6%, satisfied).
Conclusion
Patients with allergic rhinitis showed similar preferences for oral and spray medications. They also showed satisfaction with surgical treatments and an interest in the environmental management of allergic rhinitis.
8.The role of PD-1/PD-L1 pathway in ulcerative colitis and changes following tonsil-derived mesenchymal stem cells treatment
Eun Mi SONG ; Yang Hee JOO ; Sung-Ae JUNG ; Ju-Ran BYEON ; A-Reum CHOE ; Yehyun PARK ; Chung Hyun TAE ; Chang Mo MOON ; Seong-Eun KIM ; Hye-Kyung JUNG ; Ki-Nam SHIM
The Korean Journal of Internal Medicine 2024;39(6):917-930
Background/Aims:
The programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway has not been fully evaluated in inflammatory bowel disease. We evaluated PD-1/PD-L1 levels in patients with ulcerative colitis (UC) and their significance in tonsil-derived mesenchymal stem cells (TMSCs) treatment.
Methods:
Using acute and chronic murine colitis model, we measured the PD-1 and PD-L1 levels in inflamed colonic tissues pre- and post-treatment with TMSCs. We also measured PD-1 and PD-L1 levels in colonic tissues from UC patients, compared to normal controls.
Results:
In the analysis using human colonic tissues, a significant increase in the levels of PD-1 and PD-L1 was observed in the colonic mucosa of patients with UC compared with normal controls (p < 0.001 and p = 0.005, respectively). When comparing the maximal disease extent, PD-L1 levels were highest in patients with proctitis (38.5 ± 46.7), followed by left-side colitis (17.5 ± 23.1) and extensive colitis (5.2 ± 8.2) (p < 0.001). In the chronic colitis model, the level of PD-L1 was decreased (p = 0.040) and the level of PD-1 increased more than in normal controls (p = 0.047). After treatment with TMSC, significant improvements were observed in body weight, disease activity index, and colon length recovery. Additionally, the levels of PD-1 and PD-L1 were recovered; PD-L1 significantly increased (p = 0.031), while the level of PD-1 decreased (p = 0.310).
Conclusions
The altered expression of PD-1 and PD-L1 in colonic mucosa may be a possible mechanism of UC, and T-MSC-derived PD-L1 could help suppress colitis.
9.Mitochondrial Ribosomal Protein L14 Promotes Cell Growth and Invasion by Modulating Reactive Oxygen Species in Thyroid Cancer
Hae Jong KIM ; Quoc Khanh NGUYEN ; Seung-Nam JUNG ; Mi Ae LIM ; Chan OH ; Yudan PIAO ; YanLi JIN ; Ju-Hui KIM ; Young Il KIM ; Yea Eun KANG ; Jae Won CHANG ; Ho-Ryun WON ; Bon Seok KOO
Clinical and Experimental Otorhinolaryngology 2023;16(2):184-197
Objectives:
. The mitochondrial ribosomal protein L14 (MRPL14) is encoded by a nuclear gene and participates in mitochondrial protein translation. In this study, we aimed to investigate the role of MRPL14 in thyroid cancer.
Methods:
. We investigated the association between MRPL14 expression and clinicopathological features using The Cancer Genome Atlas (TCGA) and Chungnam National University Hospital (CNUH) databases. Functional studies of MRPL14, including proliferation, migration, invasion, mitochondrial oxidative phosphorylation and reactive oxygen species (ROS) production, were performed in papillary thyroid cancer (PTC) cell lines (B-CPAP and KTC-1).
Results:
. Based on the TCGA dataset, PTC tissues lost mitochondrial integrity and showed dysregulated expression of overall mitoribosomal proteins (MRPs) compared with normal thyroid tissues. Of 78 MRPs, MRPL14 was highly expressed in thyroid cancer tissues. MRPL14 overexpression was significantly associated with advanced tumor stage, extrathyroidal extension, and lymph node metastasis. MRPL14 increased cell proliferation of thyroid cancer and promoted cell migration via epithelial-mesenchymal transition-related proteins. Moreover, MRPL14 knockdown reduced the expression of oxidative phosphorylation complex IV (MTCO1) and increased the accumulation of ROS. Cotreatment with a ROS scavenger restored cell proliferation and migration, which had been reduced by MRPL14 knockdown, implying that ROS functions as a key regulator of the oncogenic effects of MRPL14 in thyroid cancer cells.
Conclusion
. Our findings indicate that MRPL14 may promote cell growth, migration, and invasion by modulating ROS in thyroid cancer cells.
10.Korea Seroprevalence Study of Monitoring of SARS-COV-2 Antibody Retention and Transmission (K-SEROSMART): findings from national representative sample
Jina HAN ; Hye Jin BAEK ; Eunbi NOH ; Kyuhyun YOON ; Jung Ae KIM ; Sukhyun RYU ; Kay O LEE ; No Yai PARK ; Eunok JUNG ; Sangil KIM ; Hyukmin LEE ; Yoo-Sung HWANG ; Jaehun JUNG ; Hun Jae LEE ; Sung-il CHO ; Sangcheol OH ; Migyeong KIM ; Chang-Mo OH ; Byengchul YU ; Young-Seoub HONG ; Keonyeop KIM ; Sunjae JUNG ; Mi Ah HAN ; Moo-Sik LEE ; Jung-Jeung LEE ; Young HWANGBO ; Hyeon Woo YIM ; Yu-Mi KIM ; Joongyub LEE ; Weon-Young LEE ; Jae-Hyun PARK ; Sungsoo OH ; Heui Sug JO ; Hyeongsu KIM ; Gilwon KANG ; Hae-Sung NAM ; Ju-Hyung LEE ; Gyung-Jae OH ; Min-Ho SHIN ; Soyeon RYU ; Tae-Yoon HWANG ; Soon-Woo PARK ; Sang Kyu KIM ; Roma SEOL ; Ki-Soo PARK ; Su Young KIM ; Jun-wook KWON ; Sung Soon KIM ; Byoungguk KIM ; June-Woo LEE ; Eun Young JANG ; Ah-Ra KIM ; Jeonghyun NAM ; ; Soon Young LEE ; Dong-Hyun KIM
Epidemiology and Health 2023;45(1):e2023075-
OBJECTIVES:
We estimated the population prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including unreported infections, through a Korea Seroprevalence Study of Monitoring of SARS-CoV-2 Antibody Retention and Transmission (K-SEROSMART) in 258 communities throughout Korea.
METHODS:
In August 2022, a survey was conducted among 10,000 household members aged 5 years and older, in households selected through two stage probability random sampling. During face-to-face household interviews, participants self-reported their health status, COVID-19 diagnosis and vaccination history, and general characteristics. Subsequently, participants visited a community health center or medical clinic for blood sampling. Blood samples were analyzed for the presence of antibodies to spike proteins (anti-S) and antibodies to nucleocapsid proteins (anti-N) SARS-CoV-2 proteins using an electrochemiluminescence immunoassay. To estimate the population prevalence, the PROC SURVEYMEANS statistical procedure was employed, with weighting to reflect demographic data from July 2022.
RESULTS:
In total, 9,945 individuals from 5,041 households were surveyed across 258 communities, representing all basic local governments in Korea. The overall population-adjusted prevalence rates of anti-S and anti-N were 97.6% and 57.1%, respectively. Since the Korea Disease Control and Prevention Agency has reported a cumulative incidence of confirmed cases of 37.8% through July 31, 2022, the proportion of unreported infections among all COVID-19 infection was suggested to be 33.9%.
CONCLUSIONS
The K-SEROSMART represents the first nationwide, community-based seroepidemiologic survey of COVID-19, confirming that most individuals possess antibodies to SARS-CoV-2 and that a significant number of unreported cases existed. Furthermore, this study lays the foundation for a surveillance system to continuously monitor transmission at the community level and the response to COVID-19.

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