1.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.
2.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.
3.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.
4.Intensified First Cycle of Rituximab Plus Eight Cycles of Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone with Rituximab Chemotherapy for Advanced-Stage or Bulky Diffuse Large B-Cell Lymphoma: A Multicenter Phase II Consortium for Improving Survival of Lymphoma (CISL) Study
Yu Ri KIM ; Jin Seok KIM ; Won Seog KIM ; Hyeon Seok EOM ; Deok-Hwan YANG ; Sung Hwa BAE ; Hyo Jung KIM ; Jae Hoon LEE ; Suk-Joong OH ; Sung-Soo YOON ; Jae-Yong KWAK ; Chul Won CHOI ; Min Kyoung KIM ; Sung Young OH ; Hye Jin KANG ; Seung Hyun NAM ; Hyeok SHIM ; Joon Seong PARK ; Yeung-Chul MUN ; Cheolwon SUH ;
Cancer Research and Treatment 2023;55(4):1355-1362
Purpose:
This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL).
Materials and Methods:
Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy.
Results:
Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016).
Conclusion
Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.
5.Clinical Practice Guideline: Nasal Irrigation for Chronic Rhinosinusitis in Adults
Do-Yang PARK ; Ji Ho CHOI ; Dong-Kyu KIM ; Yong Gi JUNG ; Sue Jean MUN ; Hyun Jin MIN ; Soo Kyoung PARK ; Jae-Min SHIN ; Hyung Chae YANG ; Seung-No HONG ; Ji-Hun MO
Clinical and Experimental Otorhinolaryngology 2022;15(1):5-23
The Korean Society of Otorhinolaryngology-Head and Neck Surgery and Korean Rhinologic Society appointed a guideline development group (GDG) to establish a clinical practice guideline, and the GDG developed a guideline for nasal irrigation for adult patients with chronic rhinosinusitis (CRS). The guideline focuses on knowledge gaps, practice variations, and clinical concerns associated with nasal irrigation. Nasal irrigation has been recommended as the first-line treatment for CRS in various guidelines, and its clinical effectiveness has been demonstrated through a number of studies with robust evidence. However, no guidelines have presented a consistent nasal irrigation method. Several databases, including OVID Medline, Embase, the Cochrane Library, and KoreaMed, were searched to identify all relevant papers using a predefined search strategy. When insufficient evidence was found, the GDG sought expert opinions and attempted to fill the evidence gap. Evidence-based recommendations for practice were ranked according to the American College of Physicians grading system. The committee developed 11 evidence-based recommendations. This guideline focuses on the evidence-based quality improvement opportunities deemed the most important by the GDG. Moreover, the guideline addresses whether nasal lavage helps treat CRS, what type of rinsing solution should be used, and the effectiveness of using additional medications to increase the therapeutic effect.
6.Long-term follow-up results of cytarabine-containing chemotherapy for acute promyelocytic leukemia
Young Hoon PARK ; Dae-Young KIM ; Yeung-Chul MUN ; Eun Kyung CHO ; Jae Hoon LEE ; Deog-Yeon JO ; Inho KIM ; Sung-Soo YOON ; Seon Yang PARK ; Byoungkook KIM ; Soo-Mee BANG ; Hawk KIM ; Young Joo MIN ; Jae Hoo PARK ; Jong Jin SEO ; Hyung Nam MOON ; Moon Hee LEE ; Chul Soo KIM ; Won Sik LEE ; So Young CHONG ; Doyeun OH ; Dae Young ZANG ; Kyung Hee LEE ; Myung Soo HYUN ; Heung Sik KIM ; Sung-Hyun KIM ; Hyukchan KWON ; Hyo Jin KIM ; Kyung Tae PARK ; Sung Hwa BAE ; Hun Mo RYOO ; Jung Hye CHOI ; Myung-Ju AHN ; Hwi-Joong YOON ; Sung-Hyun NAM ; Bong-Seog KIM ; Chu-Myong SEONG
The Korean Journal of Internal Medicine 2022;37(4):841-850
Background/Aims:
We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL).
Methods:
We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up.
Results:
The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis.
Conclusions
Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.
7.Reduced-Intensity Conditioning with Busulfan and Fludarabine for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Lymphoblastic Leukemia
Seung-Shin LEE ; Sung-Hoon JUNG ; Young Rok DO ; Dae Sik KIM ; Ji Hyun LEE ; Han-Seung PARK ; Joon Ho MOON ; Jun Ho YI ; Yong PARK ; Youngil KOH ; Ho-Young YHIM ; Yunsuk CHOI ; Yeung-Chul MUN ; Won-Sik LEE ; Seok LEE ; Deok-Hwan YANG ;
Yonsei Medical Journal 2020;61(6):452-459
Purpose:
Allogeneic hematopoietic stem cell transplantation (HSCT) with optimal conditioning has helped better long-term survival in acute lymphoblastic leukemia (ALL). This study investigated the efficacy and safety of reduced-intensity conditioning (RIC) with busulfan and fludarabine in adult ALL patients unfit for myeloablation.
Materials and Methods:
Records of 78 patients who underwent HSCT with RIC consisting of 3.2 mg/kg/day of busulfan for 2 or 3 days and 30 mg/m2/day of fludarabine for 5 or 6 days were analyzed.
Results:
The median age at diagnosis was 49 years. Over a median follow-up of 22 months, 2-year estimates of relapse-free survival (RFS) and overall survival were 57.4% and 68.7%, respectively. Multivariate analysis showed a trend of improved RFS in patients with chronic graft-versus-host disease (GVHD) (hazard ratio, 0.53; 95% confidence interval, 0.26–1.08; p=0.080). The cumulative incidences of relapse and non-relapse mortality were 42.9% and 19.6%, respectively and one case of central nervous system relapse was noted. No hepatic veno-occlusive disease was reported. Grade II–IV acute GVHD and any grade chronic GVHD occurred in 21.1% and 41.7%, respectively.
Conclusion
RIC with busulfan and fludarabine is an effective and safe conditioning regimen for adult ALL patients unfit for myeloablation.
8.Confirmation of COVID-19 in Outof-Hospital Cardiac Arrest Patients and Postmortem Management in the Emergency Department during the COVID-19 Outbreak
Changho KIM ; In Hwan YEO ; Jong Kun KIM ; Yeonjoo CHO ; Mi Jin LEE ; Haewon JUNG ; Jae Wan CHO ; Ji Yeon HAM ; Suk Hee LEE ; Han Sol CHUNG ; You Ho MUN ; Sang Hun LEE ; Yang Hun KIM ;
Infection and Chemotherapy 2020;52(4):562-572
Background:
There is currently a lack of evidence-based postresuscitation or postmortem guidelines for patients with out-of-hospital cardiac arrest (OHCA) in the setting of an emerging infectious disease. This study aimed to develop and validate a multimodal screening tool that aids in predicting the disease confirmation in emergency situations and patients with OHCA during a coronavirus disease 2019 (COVID-19) outbreak.
Materials and Methods:
We conducted a retrospective, multicenter observational study of adult patients with OHCA in Daegu, Korea. To identify the potential predictors that could be used in screening tools in the emergency department, we applied logistic regression to data collected from March 1 to March 14. The prediction performance of the screening variables was then assessed and validated on the data of patients with OHCA who were treated between February 19 and March 31, 2020. General patient characteristics and hematological findings of the COVID-19-negative and COVID-19-positive groups were compared. We also evaluated confirmation test criteria as predictors for COVID-19 positivity in patients with OHCA.
Results:
Advanced age, body temperature, and abnormal chest X-ray (CXR) revealed significant predictive ability in the derivation cohort. Of the 184 adult patients with OHCA identified in the validation cohort, 80 patients were included in the analysis. Notably, 9 patients were positive and 71 were negative on the COVID-19 reverse transcription polymerase chain reaction test. Five patients (55.6%) in the COVID-19-positive group had a fever before OHCA, and 12 (16.9%) of the COVID-19-negative group had a fever before OHCA (P = 0.018).Eight patients (88.9%) in the COVID-19-positive group had a CXR indicating pneumonic infiltration. Of the criteria for predicting COVID-19, fever or an abnormal CXR had a sensitivity of 100% (95% confidence interval [CI]: 65.4 – 100) and a specificity of 22.5% (95% CI: 13.5 – 34.0).
Conclusion
The screening tools that combined fever or abnormal CXR had a good discriminatory ability for COVID-19 infection in adult patients with OHCA. Therefore, during the COVID-19 outbreak period, it is recommended to suspect COVID-19 infection and perform COVID-19 test if patients present with a history of fever or show abnormal findings in postmortem CXR
9.Confirmation of COVID-19 in Outof-Hospital Cardiac Arrest Patients and Postmortem Management in the Emergency Department during the COVID-19 Outbreak
Changho KIM ; In Hwan YEO ; Jong Kun KIM ; Yeonjoo CHO ; Mi Jin LEE ; Haewon JUNG ; Jae Wan CHO ; Ji Yeon HAM ; Suk Hee LEE ; Han Sol CHUNG ; You Ho MUN ; Sang Hun LEE ; Yang Hun KIM ;
Infection and Chemotherapy 2020;52(4):562-572
Background:
There is currently a lack of evidence-based postresuscitation or postmortem guidelines for patients with out-of-hospital cardiac arrest (OHCA) in the setting of an emerging infectious disease. This study aimed to develop and validate a multimodal screening tool that aids in predicting the disease confirmation in emergency situations and patients with OHCA during a coronavirus disease 2019 (COVID-19) outbreak.
Materials and Methods:
We conducted a retrospective, multicenter observational study of adult patients with OHCA in Daegu, Korea. To identify the potential predictors that could be used in screening tools in the emergency department, we applied logistic regression to data collected from March 1 to March 14. The prediction performance of the screening variables was then assessed and validated on the data of patients with OHCA who were treated between February 19 and March 31, 2020. General patient characteristics and hematological findings of the COVID-19-negative and COVID-19-positive groups were compared. We also evaluated confirmation test criteria as predictors for COVID-19 positivity in patients with OHCA.
Results:
Advanced age, body temperature, and abnormal chest X-ray (CXR) revealed significant predictive ability in the derivation cohort. Of the 184 adult patients with OHCA identified in the validation cohort, 80 patients were included in the analysis. Notably, 9 patients were positive and 71 were negative on the COVID-19 reverse transcription polymerase chain reaction test. Five patients (55.6%) in the COVID-19-positive group had a fever before OHCA, and 12 (16.9%) of the COVID-19-negative group had a fever before OHCA (P = 0.018).Eight patients (88.9%) in the COVID-19-positive group had a CXR indicating pneumonic infiltration. Of the criteria for predicting COVID-19, fever or an abnormal CXR had a sensitivity of 100% (95% confidence interval [CI]: 65.4 – 100) and a specificity of 22.5% (95% CI: 13.5 – 34.0).
Conclusion
The screening tools that combined fever or abnormal CXR had a good discriminatory ability for COVID-19 infection in adult patients with OHCA. Therefore, during the COVID-19 outbreak period, it is recommended to suspect COVID-19 infection and perform COVID-19 test if patients present with a history of fever or show abnormal findings in postmortem CXR
10.Symptomatic Retinal Artery Occlusion after Angioplasty and Stenting of the Carotid Artery: Incidence and Related Risk Factors
Sang Joon AN ; Young Dae CHO ; Jeongjun LEE ; Jong Hyeon MUN ; Dong Hyun YOO ; Hyun Seung KANG ; Yun jung YANG ; Moon Hee HAN
Korean Journal of Radiology 2019;20(11):1546-1553
OBJECTIVE: Retinal artery occlusion (RAO) is rarely seen as a complication in patients undergoing carotid artery stenting (CAS); hence, its characteristics have not been documented in detail. This study aimed to investigate the incidence of this complication and the related risk factors, focusing on differences in ophthalmic artery (OA) supply (whether by the external or internal carotid artery [ECA or ICA]) prior to CAS procedures. MATERIALS AND METHODS: We retrospectively examined 342 patients who underwent CAS for severe and/or symptomatic carotid artery stenosis between January 2009 and December 2017. Cumulative medical records and radiologic data were assessed. RAO was confirmed by photography and fluorescent angiography of the fundus, which were performed by an ophthalmologist. In all patients, distal filter systems of various types were applied as cerebral protection devices (CPDs) during procedures. Univariate and multivariate analyses were conducted to identify the risk factors for RAO after CAS. RESULTS: Symptomatic RAO was observed in six patients (1.8%), of which five (6.8%) were ECA-dominant group members (n = 74). In a binary logistic regression analysis, OA supply by the ECA (odds ratio [OR], 9.705; 95% confidence interval [CI], 1.519–62.017; p = 0.016) and older age (OR, 1.159; 95% CI, 1.005–1.336; p = 0.041) were identified as significant risk factors in patients with RAO after CAS. ECA-supplied OA was also associated with the severity of ipsilateral ICA stenosis (p = 0.001) and ulcerative plaque (p = 0.021). CONCLUSION: In procedures performed using ICA distal filtering CPD systems, RAO as a complication of CAS (performed for severe stenosis) showed a relationship to ECA-supplied OA. For older patients, simultaneous use of ICA-ECA CPDs might help prevent such complications.
Angiography
;
Angioplasty
;
Carotid Arteries
;
Carotid Artery, Internal
;
Carotid Stenosis
;
Constriction, Pathologic
;
Humans
;
Incidence
;
Logistic Models
;
Medical Records
;
Multivariate Analysis
;
Ophthalmic Artery
;
Photography
;
Retinal Artery Occlusion
;
Retinal Artery
;
Retinaldehyde
;
Retrospective Studies
;
Risk Factors
;
Stents
;
Ulcer

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