1.Phytotherapeutic BS012 and Its Active Component Ameliorate Allergic Asthma via Inhibition of Th2-Mediated Immune Response and Apoptosis
Siqi ZHANG ; Joonki KIM ; Gakyung LEE ; Hong Ryul AHN ; Yeo Eun KIM ; Hee Ju KIM ; Jae Sik YU ; Miso PARK ; Keon Wook KANG ; Hocheol KIM ; Byung Hwa JUNG ; Sung Won KWON ; Dae Sik JANG ; Hyun Ok YANG
Biomolecules & Therapeutics 2024;32(6):744-758
Asthma is a chronic inflammatory disorder of the lungs that results in airway inflammation and narrowing. BS012 is an herbal remedy containing Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts. To elucidate the anti-asthma effect of BS012, this study analyzed the immune response, respiratory protection, and changes in metabolic mechanisms in an ovalbumininduced allergic asthma mouse model. Female BALB/c mice were exposed to ovalbumin to induce allergic asthma. Bronchoalveolar lavage fluid and plasma were analyzed for interleukin and immunoglobulin E levels. Histological analyses of the lungs were performed to measure morphological changes. Apoptosis-related mediators were assayed by western blotting. Plasma and lung tissue metabolomic analyses were performed to investigate the metabolic changes. A T-helper-2-like differentiated cell model was used to identify the active components of BS012. BS012 treatment improved inflammatory cell infiltration, mucus production, and goblet cell hyperplasia in lung tissues. BS012 also significantly downregulated ovalbumin-specific immunoglobulin E in plasma and T-helper-2-specific cytokines, interleukin-4 and -5, in bronchoalveolar lavage fluid. The lungs of ovalbumin-inhaled mice exhibited nerve growth factor-mediated apoptotic protein expression, which was significantly attenuated by BS012 treatment. Ovalbumin-induced abnormalities in amino acid and lipid metabolism were improved by BS012 in correlation with its anti-inflammatory properties and normalization of energy metabolism. Additionally, the differentiated cell model revealed that N-isobutyl-dodecatetraenamide is an active component that contributes to the anti-allergic properties of BS012. The current findings demonstrate the anti-allergic and respiratory protective functions of BS012 against allergic asthma, which can be considered a therapeutic candidate.
2.Phytotherapeutic BS012 and Its Active Component Ameliorate Allergic Asthma via Inhibition of Th2-Mediated Immune Response and Apoptosis
Siqi ZHANG ; Joonki KIM ; Gakyung LEE ; Hong Ryul AHN ; Yeo Eun KIM ; Hee Ju KIM ; Jae Sik YU ; Miso PARK ; Keon Wook KANG ; Hocheol KIM ; Byung Hwa JUNG ; Sung Won KWON ; Dae Sik JANG ; Hyun Ok YANG
Biomolecules & Therapeutics 2024;32(6):744-758
Asthma is a chronic inflammatory disorder of the lungs that results in airway inflammation and narrowing. BS012 is an herbal remedy containing Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts. To elucidate the anti-asthma effect of BS012, this study analyzed the immune response, respiratory protection, and changes in metabolic mechanisms in an ovalbumininduced allergic asthma mouse model. Female BALB/c mice were exposed to ovalbumin to induce allergic asthma. Bronchoalveolar lavage fluid and plasma were analyzed for interleukin and immunoglobulin E levels. Histological analyses of the lungs were performed to measure morphological changes. Apoptosis-related mediators were assayed by western blotting. Plasma and lung tissue metabolomic analyses were performed to investigate the metabolic changes. A T-helper-2-like differentiated cell model was used to identify the active components of BS012. BS012 treatment improved inflammatory cell infiltration, mucus production, and goblet cell hyperplasia in lung tissues. BS012 also significantly downregulated ovalbumin-specific immunoglobulin E in plasma and T-helper-2-specific cytokines, interleukin-4 and -5, in bronchoalveolar lavage fluid. The lungs of ovalbumin-inhaled mice exhibited nerve growth factor-mediated apoptotic protein expression, which was significantly attenuated by BS012 treatment. Ovalbumin-induced abnormalities in amino acid and lipid metabolism were improved by BS012 in correlation with its anti-inflammatory properties and normalization of energy metabolism. Additionally, the differentiated cell model revealed that N-isobutyl-dodecatetraenamide is an active component that contributes to the anti-allergic properties of BS012. The current findings demonstrate the anti-allergic and respiratory protective functions of BS012 against allergic asthma, which can be considered a therapeutic candidate.
3.Phytotherapeutic BS012 and Its Active Component Ameliorate Allergic Asthma via Inhibition of Th2-Mediated Immune Response and Apoptosis
Siqi ZHANG ; Joonki KIM ; Gakyung LEE ; Hong Ryul AHN ; Yeo Eun KIM ; Hee Ju KIM ; Jae Sik YU ; Miso PARK ; Keon Wook KANG ; Hocheol KIM ; Byung Hwa JUNG ; Sung Won KWON ; Dae Sik JANG ; Hyun Ok YANG
Biomolecules & Therapeutics 2024;32(6):744-758
Asthma is a chronic inflammatory disorder of the lungs that results in airway inflammation and narrowing. BS012 is an herbal remedy containing Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts. To elucidate the anti-asthma effect of BS012, this study analyzed the immune response, respiratory protection, and changes in metabolic mechanisms in an ovalbumininduced allergic asthma mouse model. Female BALB/c mice were exposed to ovalbumin to induce allergic asthma. Bronchoalveolar lavage fluid and plasma were analyzed for interleukin and immunoglobulin E levels. Histological analyses of the lungs were performed to measure morphological changes. Apoptosis-related mediators were assayed by western blotting. Plasma and lung tissue metabolomic analyses were performed to investigate the metabolic changes. A T-helper-2-like differentiated cell model was used to identify the active components of BS012. BS012 treatment improved inflammatory cell infiltration, mucus production, and goblet cell hyperplasia in lung tissues. BS012 also significantly downregulated ovalbumin-specific immunoglobulin E in plasma and T-helper-2-specific cytokines, interleukin-4 and -5, in bronchoalveolar lavage fluid. The lungs of ovalbumin-inhaled mice exhibited nerve growth factor-mediated apoptotic protein expression, which was significantly attenuated by BS012 treatment. Ovalbumin-induced abnormalities in amino acid and lipid metabolism were improved by BS012 in correlation with its anti-inflammatory properties and normalization of energy metabolism. Additionally, the differentiated cell model revealed that N-isobutyl-dodecatetraenamide is an active component that contributes to the anti-allergic properties of BS012. The current findings demonstrate the anti-allergic and respiratory protective functions of BS012 against allergic asthma, which can be considered a therapeutic candidate.
4.The Association between Social Support, Metabolic Syndrome, and Incidence of Cardio-Cerebrovascular Diseases in Older Adults: The ARIRANG Study
Hae-Kweun NAM ; Sei-Jin CHANG ; Chun-Bae KIM ; Kyoung Sook JEONG ; Sung-Kyung KIM ; Dae Ryong KANG ; Yong Whi JEONG ; Hocheol LEE ; Bo ZHAO ; Sang-Baek KOH
Yonsei Medical Journal 2024;65(6):363-370
Purpose:
We investigated the association between social support, metabolic syndrome, and incident cardio-cerebrovascular disease (CCVD) in rural Koreans aged ≥50 years.
Materials and Methods:
We conducted a prospective study using the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population (KoGES-ARIRANG) dataset. From the baseline of 5169 adults, 1682 participants were finally included according to the exclusion criteria. For outcomes, myocardial infarction, angina, and stroke were included. For independent variables, the social support score and metabolic syndrome were used. Descriptive statistics and multivariate logistic regression were performed to investigate the association among the variables. Paired t-test was conducted to analyze the longitudinal variation of social support scores.
Results:
During the 6.37 years of median follow-up, 137 participants developed CCVD. The adjusted odds ratio (aOR) of metabolic syndrome with persistently high social support was 2.175 [95% confidence interval (CI): 1.479–3.119]. The aOR of metabolic syndrome with persistently low social support was 2.494 (95%CI: 1.141–5.452). The longitudinal variation of the social support score of persistently high social support group was increased significantly by 4.26±26.32. The score of the persistently low social support group was decreased by 1.34±16.87 with no statistical significance.
Conclusion
The presence of metabolic syndrome increases the likelihood of developing onset CCVD. Within the metabolic syndrome positive group, when social support was persistently low, the cohort developed more cardio-cerebrovascular disease compared to the persistently higher social support group. The social support score of the persistently low social support group could be improved through proper intervention. To prevent CCVD, metabolic syndrome components and low social support should be improved in the study participants.
5.Intracellular Loop in the Brain Isoforms of Anoctamin 2 Channels Regulates Calcium-dependent Activation
Dongsu LEE ; Hocheol LIM ; Jungryun LEE ; Go Eun HA ; Kyoung Tai NO ; Eunji CHEONG
Experimental Neurobiology 2023;32(3):133-146
Anoctamin 2 (ANO2 or TMEM16B), a calcium-activated chloride channel (CaCC), performs diverse roles in neurons throughout the central nervous system. In hippocampal neurons, ANO2 narrows action potential width and reduces postsynaptic depolarization with high sensitivity to Ca2+ at relatively fast kinetics. In other brain regions, including the thalamus, ANO2 mediates activity-dependent spike frequency adaptations with low sensitivity to Ca2+ at relatively slow kinetics. How this same channel can respond to a wide range of Ca2+ levels remains unclear. We hypothesized that splice variants of ANO2 may contribute to its distinct Ca2+ sensitivity, and thus its diverse neuronal functions. We identified two ANO2 isoforms expressed in mouse brains and examined their electrophysiological properties: isoform 1 (encoded by splice variants with exons 1a, 2, 4, and 14) was expressed in the hippocampus, while isoform 2 (encoded by splice variants with exons 1a, 2, and 4) was broadly expressed throughout the brain, including in the cortex and thalamus, and had a slower calcium-dependent activation current than isoform 1. Computational modeling revealed that the secondary structure of the first intracellular loop of isoform 1 forms an entrance cavity to the calcium-binding site from the cytosol that is relatively larger than that in isoform 2. This difference provides structural evidence that isoform 2 is involved in accommodating spike frequency, while isoform 1 is involved in shaping the duration of an action potential and decreasing postsynaptic depolarization. Our study highlights the roles and molecular mechanisms of specific ANO2 splice variants in modulating neuronal functions.
6.Assessing the Fear Factor of Coronavirus Disease 2019 (COVID-19) in Korea Using the COVID-19 Phobia Scale: A Cross-Sectional Study
Hocheol LEE ; Hye Ji KIM ; Dan Hee KWON ; Myung Bae PARK ; Sang Mi KIM ; Kyeong Na KIM ; Eun Woo NAM
Journal of Korean Medical Science 2023;38(7):e52-
Background:
A study on coronavirus disease 2019 (COVID-19) phobia among students revealed that fear of contracting COVID-19 was associated with commuting to school and spending time with others at school. Therefore, it is the need-of-the-hour for the Korean government to identify factors affecting COVID-19 phobia among university students and to consider these factors while framing the policy direction for the process of returning to normalcy in university education. Consequently, we aimed to identify the current state of COVID-19 phobia among Korean undergraduate and graduate students and the factors affecting COVID-19 phobia.
Methods:
This cross-sectional survey was conducted to identify the factors affecting COVID-19 phobia among Korean undergraduate and graduate students. The survey collected 460 responses from April 5 to April 16, 2022. The questionnaire was developed based on the COVID-19 Phobia Scale (C19P-S). Multiple linear regression was performed on the C19P-S scores using five models with the following dependent variables: Model 1, total C19P-S score; Model 2, psychological subscale score; Model 3, psychosomatic subscale score; Model 4, social subscale score; and Model 5, economic subscale score. The fit of these five models was established, and a P-value of less than 0.05 (F test) was considered statistically significant.
Results:
An analysis of the factors affecting the total C19P-S score led to the following findings: women significantly outscored men (difference: 4.826 points, P = 0.003); the group that favored the government’s COVID-19 mitigation policy scored significantly lower than those who did not favor it (difference: 3.161 points, P = 0.037); the group that avoided crowded places scored significantly higher than the group that did not avoid crowded places (difference: 7.200 points, P < 0.001); and those living with family/friends scored significantly higher than those in other living situations (difference: 4.606 points, P = 0.021). Those in favor of the COVID-19 mitigation policy had significantly lower psychological fear than those who were against it (difference: -1.686 points, P = 0.004). Psychological fear was also significantly higher for those who avoided crowded places compared to those who did not difference: 2.641 points, P < 0.001). Fear was significantly higher in people cohabitating than those living alone (difference: 1.543 points, P= 0.043).
Conclusion
The Korean government, in their pursuit of a policy that eases COVID-19-related restrictions, will also have to spare no efforts in providing correct information to prevent the escalation of COVID-19 phobia among people with a high fear of contracting the disease. This should be done through trustworthy information sources, such as the media, public agencies, and COVID-19 professionals.
7.Which Group Should be Vaccinated First?: A Systematic Review
Eun Bi NOH ; Hae-Kweun NAM ; Hocheol LEE
Infection and Chemotherapy 2021;53(2):261-270
Background:
Since the supply of coronavirus disease 2019 (COVID-19) vaccines will be limited worldwide, it is essential to prioritize vaccination based on scientific evidence.Although several frameworks and studies on vaccine distribution have been published, no published systematic review has evaluated the prioritization of the COVID-19 vaccine.
Materials and Methods:
We searched 4 different databases, PubMed, SCOPUS, Web of Science, and EMBASE for articles published between January 2019 and December 31, 2020. Studies were included if they contained the primary search terms “vaccine”, “COVID-19”, and “prioritization”. In addition, we manually included reports from national and international websites.
Results:
Thirteen studies met the inclusion criteria. In these studies, older adults were the most frequently mentioned group, and healthcare workers (HCWs) were mentioned as the 1st priority group. HCWs and patients with comorbidities were the 2nd and 3rd most frequently mentioned groups in the reviewed papers. Reducing severe COVID-19 was the most frequently mentioned goal.
Conclusion
Since vaccination programs have been initiated in several countries, scientific evidence on vaccination prioritization is needed to increase our knowledge of general vaccine prioritization and improve vaccine acceptance. Our results showed that HCWs and older adults were the most frequently valued in studies.
8.European Regulatory Science and Regulatory Science Expert Training Project
Hocheol SHIN ; Jaehong PARK ; Jiwon KIM ; Dajung BAEK ; Yun-ji LEE ; Sun-Young JUNG ; Wonku KANG ; Hahyung KIM ; Young Wook CHOI ; Eunyoung KIM
Korean Journal of Clinical Pharmacy 2021;31(3):171-179
Background:
Need for regulatory science is emerging with the development of pharmaceutical industry. It is essential to train regulatory science experts to meet the needs of technology and regulations to evaluate advanced products. Major regulatory science countries are conducting the regulatory science activities and fostering the experts.
Methods:
Published literature and the relevant website of European Union (EU) were reviewed and criteria were developed. In particular, we focused on in depth descriptions of the Innovative Medicines Initiative program, which was conducted twice.
Results:
EU is striving to provide funding and training experts for the development of the regulatory science by horizon 2020 and regulatory science to 2025. Innovative medicines initiative (IMI) is a public-private partnership aimed at the development of the pharmaceutical industry, including the regulatory science. IMI education and training projects have provided various education and training course including short-term curriculum and master and doctoral course. The difference between South Korea’s regulatory science expert training project in 2021 and the EU’s IMI education and training projects is participation of pharmaceutical companies. While the pharmaceutical companies participate in the IMI project to select project topics and form a community, South Korea’s project is focused on the Ministry of Food and Drug Safety and universities.
Conclusion
Through successful active networks with regulatory party, pharmaceutical companies, and universities, a great innovative advance of regulatory science in South Korea is expected.
9.European Regulatory Science and Regulatory Science Expert Training Project
Hocheol SHIN ; Jaehong PARK ; Jiwon KIM ; Dajung BAEK ; Yun-ji LEE ; Sun-Young JUNG ; Wonku KANG ; Hahyung KIM ; Young Wook CHOI ; Eunyoung KIM
Korean Journal of Clinical Pharmacy 2021;31(3):171-179
Background:
Need for regulatory science is emerging with the development of pharmaceutical industry. It is essential to train regulatory science experts to meet the needs of technology and regulations to evaluate advanced products. Major regulatory science countries are conducting the regulatory science activities and fostering the experts.
Methods:
Published literature and the relevant website of European Union (EU) were reviewed and criteria were developed. In particular, we focused on in depth descriptions of the Innovative Medicines Initiative program, which was conducted twice.
Results:
EU is striving to provide funding and training experts for the development of the regulatory science by horizon 2020 and regulatory science to 2025. Innovative medicines initiative (IMI) is a public-private partnership aimed at the development of the pharmaceutical industry, including the regulatory science. IMI education and training projects have provided various education and training course including short-term curriculum and master and doctoral course. The difference between South Korea’s regulatory science expert training project in 2021 and the EU’s IMI education and training projects is participation of pharmaceutical companies. While the pharmaceutical companies participate in the IMI project to select project topics and form a community, South Korea’s project is focused on the Ministry of Food and Drug Safety and universities.
Conclusion
Through successful active networks with regulatory party, pharmaceutical companies, and universities, a great innovative advance of regulatory science in South Korea is expected.
10.Which Group Should be Vaccinated First?: A Systematic Review
Eun Bi NOH ; Hae-Kweun NAM ; Hocheol LEE
Infection and Chemotherapy 2021;53(2):261-270
Background:
Since the supply of coronavirus disease 2019 (COVID-19) vaccines will be limited worldwide, it is essential to prioritize vaccination based on scientific evidence.Although several frameworks and studies on vaccine distribution have been published, no published systematic review has evaluated the prioritization of the COVID-19 vaccine.
Materials and Methods:
We searched 4 different databases, PubMed, SCOPUS, Web of Science, and EMBASE for articles published between January 2019 and December 31, 2020. Studies were included if they contained the primary search terms “vaccine”, “COVID-19”, and “prioritization”. In addition, we manually included reports from national and international websites.
Results:
Thirteen studies met the inclusion criteria. In these studies, older adults were the most frequently mentioned group, and healthcare workers (HCWs) were mentioned as the 1st priority group. HCWs and patients with comorbidities were the 2nd and 3rd most frequently mentioned groups in the reviewed papers. Reducing severe COVID-19 was the most frequently mentioned goal.
Conclusion
Since vaccination programs have been initiated in several countries, scientific evidence on vaccination prioritization is needed to increase our knowledge of general vaccine prioritization and improve vaccine acceptance. Our results showed that HCWs and older adults were the most frequently valued in studies.

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