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.Contemporary Statistics of Acute Ischemic Stroke and Transient Ischemic Attack in 2021: Insights From the CRCS-K-NIH Registry
Do Yeon KIM ; Tai Hwan PARK ; Yong-Jin CHO ; Jong-Moo PARK ; Kyungbok LEE ; Minwoo LEE ; Juneyoung LEE ; Sang Yoon BAE ; Da Young HONG ; Hannah JUNG ; Eunvin KO ; Hyung Seok GUK ; Beom Joon KIM ; Jun Yup KIM ; Jihoon KANG ; Moon-Ku HAN ; Sang-Soon PARK ; Keun-Sik HONG ; Hong-Kyun PARK ; Jeong-Yoon LEE ; Byung-Chul LEE ; Kyung-Ho YU ; Mi Sun OH ; Dong-Eog KIM ; Dong-Seok GWAK ; Soo Joo LEE ; Jae Guk KIM ; Jun LEE ; Doo Hyuk KWON ; Jae-Kwan CHA ; Dae-Hyun KIM ; Joon-Tae KIM ; Kang-Ho CHOI ; Hyunsoo KIM ; Jay Chol CHOI ; Joong-Goo KIM ; Chul-Hoo KANG ; Sung-il SOHN ; Jeong-Ho HONG ; Hyungjong PARK ; Sang-Hwa LEE ; Chulho KIM ; Dong-Ick SHIN ; Kyu Sun YUM ; Kyusik KANG ; Kwang-Yeol PARK ; Hae-Bong JEONG ; Chan-Young PARK ; Keon-Joo LEE ; Jee Hyun KWON ; Wook-Joo KIM ; Ji Sung LEE ; Hee-Joon BAE ;
Journal of Korean Medical Science 2024;39(34):e278-
This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively.Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques.There has been a decrease in intravenous thrombolysis rates, from 12% in 2017–2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for noncardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.
5.Quality of Acute Stroke Care within Emergency Medical Service System in Korea: Proposal for Severe Emergency Medical Center
Kyung Bok LEE ; Ji Sung LEE ; Jeong-Yoon LEE ; Jun Yup KIM ; Han-Yeong JEONG ; Seong-Eun KIM ; Jonguk KIM ; Do Yeon KIM ; Keon-Joo LEE ; Jihoon KANG ; Beom Joon KIM ; Tae Jung KIM ; Sang Joon AN ; Jang-Hyun BAEK ; Seongheon KIM ; Hyun-Wook NAH ; Jong Yun LEE, ; Jee-Hyun KWON ; Seong Hwan AHN ; Keun-Hwa JUNG ; Hee-Kwon PARK ; Tai Hwan PARK ; Jong-Moo PARK ; Yong-Jin CHO ; Im Seok KOH ; Soo Joo LEE ; Jae-Kwan CHA ; Joung-Ho RHA ; Juneyoung LEE ; Boung Chul LEE ; In Ok BAE ; Gui Ok KIM ; Hee-Joon BAE
Journal of the Korean Neurological Association 2023;41(1):18-30
Background:
Korea recently established 70 emergency medical service areas. However, there are many concerns that medical resources for stroke could not be evenly distributed through the country. We aimed to compare the treatment quality and outcomes of acute stroke among the emergency medical service areas.
Methods:
This study analyzed the data of 28,800 patients admitted in 248 hospitals which participated in the 8th acute stroke quality assessment by Health Insurance Review and Assessment Service. Individual hospitals were regrouped into emergency service areas according to the address of the location. Assessment indicators and fatality were compared by the service areas. We defined the appropriate hospital by the performance of intravenous thrombolysis.
Results:
In seven service areas, there were no hospitals which received more than 10 stroke patients for 6 months. In nine service areas, there were no patients who underwent intravenous thrombolysis (IVT). Among 167 designated emergency medical centers, 50 hospitals (29.9%) responded that IVT was impossible 24 hours a day. There are 97 (39.1%) hospitals that meet the definitions of appropriate hospital. In 23 service areas (32.9%) had no appropriate or feasible hospitals. The fatality of service areas with stroke centers were 6.9% within 30 days and 15.6% within 1 year from stroke onset than those without stroke centers (7.7%, 16.9%, respectively).
Conclusions
There was a wide regional gap in the medical resource and the quality of treatments for acute stroke among emergency medical service areas in Korea. The poststroke fatality rate of the service areas which have stroke centers or appropriate hospitals were significantly low.
6.Annual Case Volume and One-Year Mortality for Endovascular Treatment in Acute Ischemic Stroke
Jun Yup KIM ; Jihoon KANG ; Beom Joon KIM ; Seong-Eun KIM ; Do Yeon SEONG-EUN ; Keon-Joo LEE ; Hong-Kyun PARK ; Yong-Jin CHO ; Jong-Moo PARK ; Kyung Bok LEE ; Jae-Kwan CHA ; Ji Sung LEE ; Juneyoung LEE ; Ki Hwa YANG ; Ock Ran HONG ; Ji Hyeon SHIN ; Jung Hyun PARK ; Philip B. GORELICK ; Hee-Joon BAE
Journal of Korean Medical Science 2022;37(36):e270-
Background:
The association between endovascular treatment (EVT) case volume per hospital and clinical outcomes has been reported, but the exact volume threshold has not been determined. This study aimed to examine the case volume threshold in this context.
Methods:
National audit data on the quality of acute stroke care in patients admitted via emergency department, within 7 days of onset, in hospitals that treated ≥ 10 stroke cases during the audit period were analyzed. Ischemic stroke cases treated with EVT during the last three audits (2013, 2014, and 2016) were selected for the analysis. Annual EVT case volume per hospital was estimated and analyzed as a continuous and a categorical variable (in quartiles). The primary outcome measure was 1-year mortality as a surrogate of 3-month functional outcome. As post-hoc sensitivity analysis, replication of the study results was examined using the 2018 audit data.
Results:
We analyzed 1,746 ischemic stroke cases treated with EVT in 120 acute care hospitals. The median annual EVT case volume was 12.0 cases per hospital, and mortality rates at 1 month, 3 months, and 1 year were 12.7%, 16.6%, and 23.3%, respectively. Q3 and Q4 had 33% lower odds of 1-year mortality than Q1. Adjustments were made for predetermined confounders. Annual EVT case volume cut-off value for 1-year mortality was 15 cases per year (P < 0.02). The same cut-off value was replicated in the sensitivity analysis.
Conclusion
Annual EVT case volume was associated with 1-year mortality. The volume threshold per hospital was 15 cases per year.
7.Clinical profiles of patients with surgically resected pheochromocytoma and paraganglioma
Sun Hwa LEE ; Jae-Hyeong PARK ; Ja-Yeon LEE ; Sang-Rok LEE ; Kyoung-Suk RHEE ; Jei-Keon CHAE ; Won-Ho KIM ; Ji-Young SUL ; Jin Kyung OH ; Hee-Jin KWON ; Jae-Hwan LEE ; In-Whan SEONG
The Korean Journal of Internal Medicine 2020;35(2):351-359
Background/Aims:
Pheochromocytoma and paraganglioma (PPGL) are catecholamine-producing tumors that can cause blood pressure (BP) elevation and cardiovascular complications. Clinical presentation of these tumors may be changed through widespread use of imaging studies, which enables detection of PPGLs before onset of symptoms. We investigated clinical profiles of patients with surgically resected PPGLs.
Methods:
From 2005 to 2017, 111 consecutive patients with surgically resected PPGLs in two tertiary hospitals in Korea were studied.
Results:
Mean age was 52 ± 16 years, 57 patients (51.4%) were male and 54 (48.6%) were hypertensive. Twenty-nine PPGLs (26.1%) were extra-adrenal paragangliomas. Sixteen (14.4%) and seven patients (6.3%) (Group 1, n = 23) were diagnosed during work-up of hypertension and transient cardiomyopathy respectively, and the remainder (Group 2, n = 88) were incidentalomas detected during routine abdominal imaging. Patients in the Group 1 were younger and more frequently symptomatic, and had higher BPs, heart rates and levels of urinary catecholamines than those in the Group 2. Paragangliomas were less frequent and secretion of epinephrine and metanephrine was more predominant in the Group 1 than in Group 2. After the surgical resections, 18.2% of patients still needed antihypertensive medications.
Conclusions
Out of 111 patients with surgically resected PPGLs, 88 (79.3%) were diagnosed as incidentalomas. Seven patients presented with transient cardiomyopathy and 16 with hypertension. Tumor location and secretion of catecholamine may vary depending on the presence of symptoms.
8.Acute Stroke Care in Korea in 2013–2014: National Averages and Disparities
Jun Yup KIM ; Keon-Joo LEE ; Jihoon KANG ; Beom Joon KIM ; Seong-Eun KIM ; Hyunji OH ; Hong-Kyun PARK ; Yong-Jin CHO ; Jong-Moo PARK ; Kwang-Yeol PARK ; Kyung Bok LEE ; Soo Joo LEE ; Tackeun KIM ; Ji Sung LEE ; Juneyoung LEE ; Ki Hwa YANG ; Ah Rum CHOI ; Mi Yeon KANG ; Hee-Joon BAE
Journal of Korean Medical Science 2020;35(20):e167-
Background:
This study aimed to describe the current status of acute stroke care in Korea and explore disparities among hospitals and regions.
Methods:
The 2013 and 2014 national stroke audit data and the national health insurance claims data were linked and used for this study. Stroke patients hospitalized via emergency rooms within 7 days of stroke onset were selected.
Results:
A total of 19,608 patients treated in 216 hospitals were analyzed. Among them 76% had ischemic stroke; 15%, intracerebral hemorrhage (ICH); and 9%, subarachnoid hemorrhage (SAH). Of the hospitals, 31% provided inpatient stroke unit care. Ambulances were used in 56% of cases, and the median interval from onset to arrival was 4.5 hours. One-quarter of patients were referred from other hospitals. Intravenous thrombolysis (IVT) and endovascular treatment (EVT) rates were 11% and 4%, respectively. Three-quarters of the analyzed hospitals provided IVT and/or EVT, whereas 47% of hospitals providing IVT and 67% of hospitals providing EVT had less than one case per month. Decompressive surgery was performed on 28% of ICH patients, and clipping and coiling were performed in 17.2% and 14.3% of SAH patients, respectively. There were noticeable regional disparities between the various interventions, ambulance use, arrival time, and stroke unit availability.
Conclusion
This study describes the current status of acute stroke care in Korea. Despite quite acceptable quality of stroke care, it suggests regional and hospital disparities. Expansion of stroke units, stroke center certification or accreditation, and connections between stroke centers and emergency medical services are highly recommended.
9.Routing to Endovascular Treatment of Ischemic Stroke in Korea: Recognition of Need for Process Improvement
Jihoon KANG ; Seong-Eun KIM ; Hong-Kyun PARK ; Yong-Jin CHO ; Jun Yup KIM ; Keon-Joo LEE ; Jong-Moo PARK ; Kwang-Yeol PARK ; Kyung Bok LEE ; Soo Joo LEE ; Ji Sung LEE ; Juneyoung LEE ; Ki Hwa YANG ; Ah Rum CHOI ; Mi Yeon KANG ; Nack-Cheon CHOI ; Philip B. GORELICK ; Hee-Joon BAE
Journal of Korean Medical Science 2020;35(41):e347-
Background:
To track triage, routing, and treatment status regarding access to endovascular treatment (EVT) after acute ischemic stroke (AIS) at a national level.
Methods:
From national stroke audit data, potential candidates for EVT arriving within 6 hours with National Institute of Health Stroke Scale score of ≥ 7 were identified. Acute care hospitals were classified as thrombectomy-capable hospitals (TCHs, ≥ 15 EVT cases/year) or primary stroke hospital (PSH, < 15 cases/year), and patients' initial routes and subsequent inter-hospital transfer were described. Impact of initial routing to TCHs vs. PSHs on EVT and clinical outcomes were analyzed using multilevel generalized mixed effect models.
Results:
Out of 14,902 AIS patients, 2,180 (14.6%) were EVT candidates. Eighty-one percent of EVT candidates were transported by ambulance, but only one-third were taken initially to TCHs. Initial routing to TCHs was associated with greater chances of receiving EVT compared to initial routing to PSHs (33.3% vs 12.1%, P < 0.001; adjusted odds ratio [aOR], 2.21; 95% confidence interval [CI], 1.59–2.92) and favorable outcome (38.5% vs. 28.2%, P < 0.001; aOR, 1.52; 95% CI, 1.16–2.00). Inter-hospital transfers to TCHs occurred in 17.4% of those initially routed to a PSH and was associated with the greater chance of EVT compared to remaining at PSHs (34.8% vs. 7.5%, P < 0.001), but not with better outcomes.
Conclusion
Two-thirds of EVT candidates were initially routed to PSHs despite greater chance of receiving EVT and having favorable outcomes if routed to a TCH in Korea. Process improvement is needed to direct appropriate patients to TCHs.
10.Ramosetron versus Palonosetron in Combination with Aprepitant and Dexamethasone for the Control of Highly-Emetogenic Chemotherapy-Induced Nausea and Vomiting
Jin Hyoung KANG ; Jung Hye KWON ; Yun-Gyoo LEE ; Keon Uk PARK ; Ho Jung AN ; Joohyuk SOHN ; Young Mi SEOL ; Hyunwoo LEE ; Hwan-Jung YUN ; Jin Seok AHN ; Ji Hyun YANG ; Hunho SONG ; Dong-Hoe KOO ; Jin Young KIM ; Gun Min KIM ; Hwa Jung KIM
Cancer Research and Treatment 2020;52(3):907-916
Purpose:
The purpose of this study was to compare ramosetron (RAM), aprepitant (APR), and dexamethasone (DEX) [RAD] with palonosetron (PAL), APR, and DEX [PAD] in controlling highly-emetogenic chemotherapy (HEC)–induced nausea and vomiting.
Materials and Methods:
Patients were randomly assigned (1:1) to receive RAD or PAD:RAM (0.3 mg intravenously) or PAL (0.25 mg intravenously) D1, combined with APR (125 mg orally, D1 and 80 mg orally, D2-3) and DEX (12 mg orally or intravenously, D1 and 8 mg orally, D2-4). Patients were stratified by gender, cisplatin-based chemotherapy, and administration schedule. The primary endpoint was overall complete response (CR), defined as no emesis and no rescue regimen during 5 days of HEC. Secondary endpoints were overall complete protection (CP; CR+nausea score < 25 mm) and total control (TC; CR+nausea score < 5 mm). Quality of life was assessed by Functional Living Index Emesis (FLIE) questionnaire on D0 and D6.
Results:
A total of 279 patients receiving RAD (n=137) or PAD (n=142) were evaluated. Overall CR rates in RAD and PAD recipients were 81.8% and 79.6% (risk difference [RD], 2.2%; 95% confidence interval [CI], −7.1 to 11.4), respectively. Overall CP and TC rates for RAD and PAD were 56.2% and 58.5% (RD, −2.3%; 95% CI, −13.9 to 9.4) and 47.5% vs. 43.7% (RD, 3.8%; 95% CI, −7.9 to 15.5), respectively. FLIE total score ≥ 108 (no impact on daily life) was comparable between RAD and PAD (73.9% vs. 73.4%, respectively). Adverse events were similar between the two groups.
Conclusion
In all aspects of efficacy, safety and QOL, RAD is non-inferior to PAD for the control of CINV in cancer patients receiving HEC.

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