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.Corrigendum: Korean treatment recommendations for patients with axial spondyloarthritis
Mi Ryoung SEO ; Jina YEO ; Jun Won PARK ; Yeon-Ah LEE ; Ju Ho LEE ; Eun Ha KANG ; Seon Mi JI ; Seong-Ryul KWON ; Seong-Kyu KIM ; Tae-Jong KIM ; Tae-Hwan KIM ; Hye Won KIM ; Min-Chan PARK ; Kichul SHIN ; Sang-Hoon LEE ; Eun Young LEE ; Hoon Suk CHA ; Seung Cheol SHIM ; Youngim YOON ; Seung Ho LEE ; Jun Hong LIM ; Han Joo BAEK ;
Journal of Rheumatic Diseases 2024;31(1):62-63
5.Korean treatment recommendations for patients with axial spondyloarthritis
Mi Ryoung SEO ; Jina YEO ; Jun Won PARK ; Yeon-Ah LEE ; Ju Ho LEE ; Eun Ha KANG ; Seon Mi JI ; Seong-Ryul KWON ; Seong-Kyu KIM ; Tae-Jong KIM ; Tae-Hwan KIM ; Hye Won KIM ; Min-Chan PARK ; Kichul SHIN ; Sang-Hoon LEE ; Eun Young LEE ; Hoon Suk CHA ; Seung Cheol SHIM ; Youngim YOON ; Seung Ho LEE ; Jun Hong LIM ; Han Joo BAEK ;
The Korean Journal of Internal Medicine 2024;39(1):200-200
6.The Role of Adjuvant Therapy Following Surgical Resection of Small Cell Lung Cancer: A Multi-Center Study
Seong Yong PARK ; Samina PARK ; Geun Dong LEE ; Hong Kwan KIM ; Sehoon CHOI ; Hyeong Ryul KIM ; Yong-Hee KIM ; Dong Kwan KIM ; Seung-Il PARK ; Tae Hee HONG ; Yong Soo CHOI ; Jhingook KIM ; Jong Ho CHO ; Young Mog SHIM ; Jae Ill ZO ; Kwon Joong NA ; In Kyu PARK ; Chang Hyun KANG ; Young-Tae KIM ; Byung Jo PARK ; Chang Young LEE ; Jin Gu LEE ; Dae Joon KIM ; Hyo Chae PAIK
Cancer Research and Treatment 2023;55(1):94-102
Purpose:
This multi-center, retrospective study was conducted to evaluate the long-term survival in patients who underwent surgical resection for small cell lung cancer (SCLC) and to identify the benefit of adjuvant therapy following surgery.
Materials and Methods:
The data of 213 patients who underwent surgical resection for SCLC at four institutions were retrospectively reviewed. Patients who received neoadjuvant therapy or an incomplete resection were excluded.
Results:
The mean patient age was 65.29±8.93 years, and 184 patients (86.4%) were male. Lobectomies and pneumonectomies were performed in 173 patients (81.2%), and 198 (93%) underwent systematic mediastinal lymph node dissections. Overall, 170 patients (79.8%) underwent adjuvant chemotherapy, 42 (19.7%) underwent radiotherapy to the mediastinum, and 23 (10.8%) underwent prophylactic cranial irradiation. The median follow-up period was 31.08 months (interquartile range, 13.79 to 64.52 months). The 5-year overall survival (OS) and disease-free survival were 53.4% and 46.9%, respectively. The 5-year OS significantly improved after adjuvant chemotherapy in all patients (57.4% vs. 40.3%, p=0.007), and the survival benefit of adjuvant chemotherapy was significant in patients with negative node pathology (70.8% vs. 39.7%, p=0.004). Adjuvant radiotherapy did not affect the 5-year OS (54.6% vs. 48.5%, p=0.458). Age (hazard ratio [HR], 1.032; p=0.017), node metastasis (HR, 2.190; p < 0.001), and adjuvant chemotherapy (HR, 0.558; p=0.019) were associated with OS.
Conclusion
Adjuvant chemotherapy after surgical resection in patients with SCLC improved the OS, though adjuvant radiotherapy to the mediastinum did not improve the survival or decrease the locoregional recurrence rate.
7.Safety and Efficacy of Everolimus-Eluting Bioresorbable Vascular Scaffold Versus Second-Generation Drug-Eluting Stents in Real-World Practice
Joo Myung LEE ; Hyun Sung JOH ; Ki Hong CHOI ; David HONG ; Taek Kyu PARK ; Jeong Hoon YANG ; Young Bin SONG ; Jin-Ho CHOI ; Seung-Hyuk CHOI ; Jin-Ok JEONG ; Jong-Young LEE ; Young Jin CHOI ; Jei-Keon CHAE ; Seung-Ho HUR ; Jang-Whan BAE ; Ju-Hyeon OH ; Kook-Jin CHUN ; Hyun-Joong KIM ; Byung Ryul CHO ; Doosup SHIN ; Seung Hun LEE ; Doyeon HWANG ; Hyun-Jong LEE ; Ho-Jun JANG ; Hyun Kuk KIM ; Sang Jin HA ; Eun-Seok SHIN ; Joon-Hyung DOH ; Joo-Yong HAHN ; Hyeon-Cheol GWON ; On behalf of the SMART-REWARD Investigators
Journal of Korean Medical Science 2023;38(5):e34-
Background:
The risk of device thrombosis and device-oriented clinical outcomes with bioresorbable vascular scaffold (BVS) was reported to be significantly higher than with contemporary drug-eluting stents (DESs). However, optimal device implantation may improve clinical outcomes in patients receiving BVS. The current study evaluated mid-term safety and efficacy of Absorb BVS with meticulous device optimization under intravascular imaging guidance.
Methods:
The SMART-REWARD and PERSPECTIVE-PCI registries in Korea prospectively enrolled 390 patients with BVS and 675 patients with DES, respectively. The primary endpoint was target vessel failure (TVF) at 2 years and the secondary major endpoint was patientoriented composite outcome (POCO) at 2 years.
Results:
Patient-level pooled analysis evaluated 1,003 patients (377 patients with BVS and 626 patients with DES). Mean scaffold diameter per lesion was 3.24 ± 0.30 mm in BVS group.Most BVSs were implanted with pre-dilatation (90.9%), intravascular imaging guidance (74.9%), and post-dilatation (73.1%) at proximal to mid segment (81.9%) in target vessel.Patients treated with BVS showed comparable risks of 2-year TVF (2.9% vs. 3.7%, adjusted hazard ratio [HR], 1.283, 95% confidence interval [CI], 0.487–3.378, P = 0.615) and 2-year POCO (4.5% vs. 5.9%, adjusted HR, 1.413, 95% CI, 0.663–3.012,P = 0.370) than those with DES. The rate of 2-year definite or probable device thrombosis (0.3% vs. 0.5%, P = 0.424) was also similar. The sensitivity analyses consistently showed comparable risk of TVF and POCO between the 2 groups.
Conclusion
With meticulous device optimization under imaging guidance and avoidance of implantation in small vessels, BVS showed comparable risks of 2-year TVF and device thrombosis with DES.
8.Korean treatment recommendations for patients with axial spondyloarthritis
Mi Ryoung SEO ; Jina YEO ; Jun Won PARK ; Yeon-Ah LEE ; Ju Ho LEE ; Eun Ha KANG ; Seon Mi JI ; Seong-Ryul KWON ; Seong-Kyu KIM ; Tae-Jong KIM ; Tae-Hwan KIM ; Hye Won KIM ; Min-Chan PARK ; Kichul SHIN ; Sang-Hoon LEE ; Eun Young LEE ; Hoon Suk CHA ; Seung Cheol SHIM ; Youngim YOON ; Seung Ho LEE ; Jun Hong LIM ; Han Joo BAEK ;
Journal of Rheumatic Diseases 2023;30(3):151-169
We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and KMbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5~12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors.Recommendations 13~16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.
9.Korean treatment recommendations for patients with axial spondyloarthritis
Mi Ryoung SEO ; Jina YEO ; Jun Won PARK ; Yeon-Ah LEE ; Ju Ho LEE ; Eun Ha KANG ; Seon Mi JI ; Seong-Ryul KWON ; Seong-Kyu KIM ; Tae-Jong KIM ; Tae-Hwan KIM ; Hye Won KIM ; Min-Chan PARK ; Kichul SHIN ; Sang-Hoon LEE ; Eun Young LEE ; Hoon Suk CHA ; Seung Cheol SHIM ; Youngim YOON ; Seung Ho LEE ; Jun Hong LIM ; Han Joo BAEK ;
The Korean Journal of Internal Medicine 2023;38(5):620-640
We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and Kmbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5–12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors. Recommendations 13–16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.
10.Cyclic Phytosphingosine-1-Phosphate Primed Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice
Youngheon PARK ; Jimin JANG ; Jooyeon LEE ; Hyosin BAEK ; Jaehyun PARK ; Sang-Ryul CHA ; Se Bi LEE ; Sunghun NA ; Jae-Woo KWON ; Seok-Ho HONG ; Se-Ran YANG
International Journal of Stem Cells 2023;16(2):191-201
Background and Objectives:
O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung.Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice.
Methods:
and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSCcP1P ), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSCcP1P reduce inflammatory response in LPS exposed mice. hdMSCcP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSCcP1P treated mice.
Conclusions
Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSCcP1P provide a therapeutic potential for ALI/ARDS treatment.

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