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.Learning Curve of Autologous Arteriovenous Fistula Formation for Junior Vascular Surgeons
Mun Chae CHOI ; Seung Hyuk YIM ; Seong Wook SHIN ; Seok Jeong YANG ; Deok-Gie KIM ; Seon-Hee HEO ; Soo Jin KIM
Vascular Specialist International 2024;40(4):37-
Purpose:
Autologous arteriovenous fistulas (AVFs) are considered the gold standard for hemodialysis access, with outcomes largely dependent on the surgeon’s experience. Nevertheless, few studies have been conducted on the learning curve of junior vascular surgeons in AVF creation. This study aims to address this by examining the development of surgical skills among junior vascular surgeons.
Materials and Methods:
A retrospective analysis was conducted on 100 patients who underwent autologous AVF procedures performed by five junior surgeons between January 2018 and December 2023. To establish the cutoff number of cases for the learning curve, we examined the cubic spline curve using the hazard ratio for primary failure.
Results:
The cutoff number for operation cases was 15.33, and we divided the analysis into a pre-learning curve period (≤15 cases of AVF) and a post-learning curve period (>15 cases of AVF). The 1-year primary patency rate for AVF during the post-learning curve period was 84.0%, which was higher than the 65.5% rate observed during the pre-learning curve period. In a subgroup analysis based on AVF type, the radiocephalic fistula patient group demonstrated a significant increase in 1-year primary patency in the post-learning curve period compared to that in the pre-learning curve period (80.0% vs. 43.0%, log-rank P=0.033). In contrast, there was no significant difference in the primary patency rates between the post- and pre-learning curve periods in the brachiocephalic fistula patient group (90.0% vs. 89.2%, log-rank P=0.930).
Conclusion
Junior vascular surgeons demonstrated improved primary AVF patency beyond the learning curve benchmark in 15 patients, with particularly notable enhancements in radiocephalic fistulas.
5.Learning Curve of Autologous Arteriovenous Fistula Formation for Junior Vascular Surgeons
Mun Chae CHOI ; Seung Hyuk YIM ; Seong Wook SHIN ; Seok Jeong YANG ; Deok-Gie KIM ; Seon-Hee HEO ; Soo Jin KIM
Vascular Specialist International 2024;40(4):37-
Purpose:
Autologous arteriovenous fistulas (AVFs) are considered the gold standard for hemodialysis access, with outcomes largely dependent on the surgeon’s experience. Nevertheless, few studies have been conducted on the learning curve of junior vascular surgeons in AVF creation. This study aims to address this by examining the development of surgical skills among junior vascular surgeons.
Materials and Methods:
A retrospective analysis was conducted on 100 patients who underwent autologous AVF procedures performed by five junior surgeons between January 2018 and December 2023. To establish the cutoff number of cases for the learning curve, we examined the cubic spline curve using the hazard ratio for primary failure.
Results:
The cutoff number for operation cases was 15.33, and we divided the analysis into a pre-learning curve period (≤15 cases of AVF) and a post-learning curve period (>15 cases of AVF). The 1-year primary patency rate for AVF during the post-learning curve period was 84.0%, which was higher than the 65.5% rate observed during the pre-learning curve period. In a subgroup analysis based on AVF type, the radiocephalic fistula patient group demonstrated a significant increase in 1-year primary patency in the post-learning curve period compared to that in the pre-learning curve period (80.0% vs. 43.0%, log-rank P=0.033). In contrast, there was no significant difference in the primary patency rates between the post- and pre-learning curve periods in the brachiocephalic fistula patient group (90.0% vs. 89.2%, log-rank P=0.930).
Conclusion
Junior vascular surgeons demonstrated improved primary AVF patency beyond the learning curve benchmark in 15 patients, with particularly notable enhancements in radiocephalic fistulas.
6.Learning Curve of Autologous Arteriovenous Fistula Formation for Junior Vascular Surgeons
Mun Chae CHOI ; Seung Hyuk YIM ; Seong Wook SHIN ; Seok Jeong YANG ; Deok-Gie KIM ; Seon-Hee HEO ; Soo Jin KIM
Vascular Specialist International 2024;40(4):37-
Purpose:
Autologous arteriovenous fistulas (AVFs) are considered the gold standard for hemodialysis access, with outcomes largely dependent on the surgeon’s experience. Nevertheless, few studies have been conducted on the learning curve of junior vascular surgeons in AVF creation. This study aims to address this by examining the development of surgical skills among junior vascular surgeons.
Materials and Methods:
A retrospective analysis was conducted on 100 patients who underwent autologous AVF procedures performed by five junior surgeons between January 2018 and December 2023. To establish the cutoff number of cases for the learning curve, we examined the cubic spline curve using the hazard ratio for primary failure.
Results:
The cutoff number for operation cases was 15.33, and we divided the analysis into a pre-learning curve period (≤15 cases of AVF) and a post-learning curve period (>15 cases of AVF). The 1-year primary patency rate for AVF during the post-learning curve period was 84.0%, which was higher than the 65.5% rate observed during the pre-learning curve period. In a subgroup analysis based on AVF type, the radiocephalic fistula patient group demonstrated a significant increase in 1-year primary patency in the post-learning curve period compared to that in the pre-learning curve period (80.0% vs. 43.0%, log-rank P=0.033). In contrast, there was no significant difference in the primary patency rates between the post- and pre-learning curve periods in the brachiocephalic fistula patient group (90.0% vs. 89.2%, log-rank P=0.930).
Conclusion
Junior vascular surgeons demonstrated improved primary AVF patency beyond the learning curve benchmark in 15 patients, with particularly notable enhancements in radiocephalic fistulas.
7.Learning Curve of Autologous Arteriovenous Fistula Formation for Junior Vascular Surgeons
Mun Chae CHOI ; Seung Hyuk YIM ; Seong Wook SHIN ; Seok Jeong YANG ; Deok-Gie KIM ; Seon-Hee HEO ; Soo Jin KIM
Vascular Specialist International 2024;40(4):37-
Purpose:
Autologous arteriovenous fistulas (AVFs) are considered the gold standard for hemodialysis access, with outcomes largely dependent on the surgeon’s experience. Nevertheless, few studies have been conducted on the learning curve of junior vascular surgeons in AVF creation. This study aims to address this by examining the development of surgical skills among junior vascular surgeons.
Materials and Methods:
A retrospective analysis was conducted on 100 patients who underwent autologous AVF procedures performed by five junior surgeons between January 2018 and December 2023. To establish the cutoff number of cases for the learning curve, we examined the cubic spline curve using the hazard ratio for primary failure.
Results:
The cutoff number for operation cases was 15.33, and we divided the analysis into a pre-learning curve period (≤15 cases of AVF) and a post-learning curve period (>15 cases of AVF). The 1-year primary patency rate for AVF during the post-learning curve period was 84.0%, which was higher than the 65.5% rate observed during the pre-learning curve period. In a subgroup analysis based on AVF type, the radiocephalic fistula patient group demonstrated a significant increase in 1-year primary patency in the post-learning curve period compared to that in the pre-learning curve period (80.0% vs. 43.0%, log-rank P=0.033). In contrast, there was no significant difference in the primary patency rates between the post- and pre-learning curve periods in the brachiocephalic fistula patient group (90.0% vs. 89.2%, log-rank P=0.930).
Conclusion
Junior vascular surgeons demonstrated improved primary AVF patency beyond the learning curve benchmark in 15 patients, with particularly notable enhancements in radiocephalic fistulas.
8.Learning Curve of Autologous Arteriovenous Fistula Formation for Junior Vascular Surgeons
Mun Chae CHOI ; Seung Hyuk YIM ; Seong Wook SHIN ; Seok Jeong YANG ; Deok-Gie KIM ; Seon-Hee HEO ; Soo Jin KIM
Vascular Specialist International 2024;40(4):37-
Purpose:
Autologous arteriovenous fistulas (AVFs) are considered the gold standard for hemodialysis access, with outcomes largely dependent on the surgeon’s experience. Nevertheless, few studies have been conducted on the learning curve of junior vascular surgeons in AVF creation. This study aims to address this by examining the development of surgical skills among junior vascular surgeons.
Materials and Methods:
A retrospective analysis was conducted on 100 patients who underwent autologous AVF procedures performed by five junior surgeons between January 2018 and December 2023. To establish the cutoff number of cases for the learning curve, we examined the cubic spline curve using the hazard ratio for primary failure.
Results:
The cutoff number for operation cases was 15.33, and we divided the analysis into a pre-learning curve period (≤15 cases of AVF) and a post-learning curve period (>15 cases of AVF). The 1-year primary patency rate for AVF during the post-learning curve period was 84.0%, which was higher than the 65.5% rate observed during the pre-learning curve period. In a subgroup analysis based on AVF type, the radiocephalic fistula patient group demonstrated a significant increase in 1-year primary patency in the post-learning curve period compared to that in the pre-learning curve period (80.0% vs. 43.0%, log-rank P=0.033). In contrast, there was no significant difference in the primary patency rates between the post- and pre-learning curve periods in the brachiocephalic fistula patient group (90.0% vs. 89.2%, log-rank P=0.930).
Conclusion
Junior vascular surgeons demonstrated improved primary AVF patency beyond the learning curve benchmark in 15 patients, with particularly notable enhancements in radiocephalic fistulas.
9.Clinical effects of non-pharmaceutical interventions for COVID-19 on other nationally notifiable infectious diseases in South Korea
Hyun-Jin LEE ; Beom Seuk HWANG ; Seong Ho IM ; Seog-Kyun MUN ; Munyoung CHANG
The Korean Journal of Internal Medicine 2024;39(5):823-832
Background/Aims:
This study aimed to assess the impact of non-pharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic on nationally notifiable infectious diseases (NNIDs) in South Korea.
Methods:
Long-term data on seven NNIDs from 2018 to 2021 were analyzed to identify trends and change points using a change point detection technique. The timings of the NPI implementations were compared to the identified change points to determine their association.
Results:
Varicella, mumps, and scarlet fever showed a significant decrease in incidence following the implementation of NPIs during the COVID-19 pandemic. These diseases, which are primarily transmitted through respiratory droplets, demonstrated a clear response to NPIs. However, carbapenem-resistant Enterobacterales (CRE) showed an increasing trend unrelated to the timing of NPI implementation, suggesting the complex nature of controlling healthcare-associated infections. Hepatitis A, hepatitis C, and scrub typhus did not show significant changes associated with NPIs, likely due to their non-respiratory route of transmission.
Conclusions
NPIs effectively controlled NNIDs, particularly those transmitted through respiratory infections. However, the impact varied depending on the disease. Understanding the effectiveness and limitations of NPIs is crucial for developing comprehensive public health strategies during infectious disease outbreaks.
10.Dual alarmin-receptor-specific targeting peptide systems for treatment of sepsis.
Seok-Jun MUN ; Euni CHO ; Woo Jin GIL ; Seong Jae KIM ; Hyo Keun KIM ; Yu Seong HAM ; Chul-Su YANG
Acta Pharmaceutica Sinica B 2024;14(12):5451-5463
The pathophysiology of sepsis is characterized by a systemic inflammatory response to infection; however, the cytokine blockade that targets a specific early inflammatory mediator, such as tumor necrosis factor, has shown disappointing results in clinical trials. During sepsis, excessive endotoxins are internalized into the cytoplasm of immune cells, resulting in dysregulated pyroptotic cell death, which induces the leakage of late mediator alarmins such as HMGB1 and PTX3. As late mediators of lethal sepsis, overwhelming amounts of alarmins bind to high-affinity TLR4/MD2 and low-affinity RAGE receptors, thereby amplifying inflammation during early-stage sepsis. In this study, we developed a novel alarmin/receptor-targeting system using a TLR4/MD2/RAGE-blocking peptide (TMR peptide) derived from the HMGB1/PTX3-receptors interacting motifs. The TMR peptide successfully attenuated HMGB1/PTX3- and LPS-mediated inflammatory cytokine production by impairing its interactions with TLR4 and RAGE. Moreover, we developed TMR peptide-conjugated liposomes (TMR-Lipo) to improve the peptide pharmacokinetics. In combination therapy, moderately antibiotic-loaded TMR-Lipo demonstrated a significant therapeutic effect in a mouse model of cecal ligation- and puncture-induced sepsis. The identification of these peptides will pave the way for the development of novel pharmacological tools for sepsis therapy.

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