1.Arctigenin induces caspase-dependent apoptosis in FaDu human pharyngeal carcinoma cells
Kyeong-Rok KANG ; Jae-Sung KIM ; HyangI LIM ; Jeong-Yeon SEO ; Jong-Hyun PARK ; Hong Sung CHUN ; Sun-Kyoung YU ; Heung-Joong KIM ; Chun Sung KIM ; Do Kyung KIM
The Korean Journal of Physiology and Pharmacology 2022;26(6):447-456
The present study was carried out to investigate the effect of Arctigenin on cell growth and the mechanism of cell death elicited by Arctigenin were examined in FaDu human pharyngeal carcinoma cells. To determine the apoptotic activity of Arctigenin in FaDu human pharyngeal carcinoma cells, cell viability assay, DAPI staining, caspase activation analysis, and immunoblotting were performed. Arctigenin inhibited the growth of cells in a dose-dependent manner and induced nuclear condensation and fragmentation. Arctigenin-treated cells showed caspase-3/7 activation and increased apoptosis versus control cells. FasL, a death ligand associated with extrinsic apoptotic signaling pathways, was up-regulated by Arctigenin treatment. Moreover, caspase-8, a part of the extrinsic apoptotic pathway, was activated by Arctigenin treatments. Expressions of anti-apoptotic factors such as Bcl-2 and Bcl-xL, components of the mitochondria-dependent intrinsic apoptosis pathway, significantly decreased following Arctigenin treatment. The expressions of pro-apoptotic factors such as BAX, BAD and caspase-9, and tumor suppressor -53 increased by Arctigenin treatments. In addition, Arctigenin activated caspase-3 and poly (ADP-ribose) polymerase (PARP) induced cell death. Arctigenin also inhibited the proliferation of FaDu cells by the suppression of p38, NF-κB, and Akt signaling pathways. These results suggest that Arctigenin may inhibit cell proliferation and induce apoptotic cell death in FaDu human pharyngeal carcinoma cells through both the mitochondria-mediated intrinsic pathway and the death receptormediated extrinsic pathway.
2.Development of a house dust mite-induced mouse model for allergen-specific immunotherapy in allergic rhinitis
Seok Min KIM ; Ji An KIM ; Hwan Soo KIM ; Jong-Seo YOON ; Hyun Hee KIM ; Yoon Hong CHUN
Allergy, Asthma & Respiratory Disease 2022;10(4):195-201
Purpose:
Allergen-specific immunotherapy (AIT) is the only known curative treatment for allergic diseases. Recently, novel immunotherapies have been developed to overcome the inconvenience and adverse reactions associated with conventional AIT. Validated animal models are essential for screening novel immunotherapies; however, effective models for AIT in allergic rhinitis (AR) are lacking. Herein, we aimed to develop an optimal protocol for AIT using a house dust mite (HDM)-induced AR mouse model.
Methods:
BALB/c mice were intraperitoneally injected with the alum-absorbed HDM extract (5 µg) on days 0, 7, and 14. Sensitized mice were administered three subcutaneous injections of HDM extract (250 µg/100 µL; SCIT group) and phosphate-buffered saline (100 µL; negative and positive control groups) at 2-day intervals. Next, HDM extract (25 µg) was intranasally administered to SCIT and positive control groups for five consecutive days. Nasal symptoms, ear swelling, eosinophil count, antibody levels, and nasal mucosa histopathology were assessed in all groups. Cytokine production was analyzed in the splenocyte culture supernatant.
Results:
Compared with the positive control group, the SCIT group exhibited reduced nasal symptoms, ear swelling, and eosinophil count in nasopharyngeal lavage. Compared with the positive control group, the SCIT group had reduced eosinophil, mast cell, and goblet cell counts in the nasal mucosa. Serum levels of HDM-specific IgG1 were higher in the SCIT group than in the positive control group. The stimulation index of splenocytes was reduced in the SCIT group when compared with that in the positive control group.Compared with the positive control group, the SCIT group exhibited decreased levels of interleukin (IL)-4 and IL-17, whereas those of IL-10 and interferon-gamma levels were increased.
Conclusion
AR mice treated with the AIT-HDM protocol showed attenuated nasal symptoms and improved histopathological findings and cytokine profiles compared with the untreated AR mice. Our findings suggest that the examined model may be useful for screening new AITs.
3.Establishment of Pediatric Reference Intervals for Routine Laboratory Tests in Korean Population: A Retrospective Multicenter Analysis
Ji Yeon SUNG ; Jong Do SEO ; Dae-Hyun KO ; Min-Jeong PARK ; Sang Mee HWANG ; Sohee OH ; Sail CHUN ; Moon-Woo SEONG ; Junghan SONG ; Sang Hoon SONG ; Sung Sup PARK
Annals of Laboratory Medicine 2021;41(2):155-170
Background:
Reference intervals defined for adults or children of other ethnicities cannot be applied in the evaluation of Korean pediatric patients. Pediatric reference intervals are difficult to establish because children are in their growing stage and their physiology changes continuously. We aimed to establish reference intervals for routine laboratory tests for Korean pediatric patients through retrospective multicenter data analysis.
Methods:
Preoperative laboratory test results from 1,031 pediatric patients aged 0 month–18 years who underwent minor surgeries in four university hospitals were collected. Age- and sex-specific reference intervals for routine laboratory tests were defined based on the Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines.
Results:
The pediatric reference intervals determined in this study were different from existing adult reference intervals and pediatric reference intervals for other ethnicities. Most tests required age-specific partitioning, and some of those required sex-specific partitioning for at least one age-partitioned subgroup. Erythrocyte sedimentation rate, monocyte percentage, basophil percentage, activated partial thromboplastin time, glucose, cholesterol, albumin, bilirubin, chloride, and C-reactive protein did not show any difference between age- or sex-partitioned subgroups.
Conclusions
We determined Korean pediatric reference intervals for hematology, coagulation, and chemistry tests by indirect sampling based on medical record data from multiple institutions. These reference intervals would be valuable for clinical evaluations in the Korean pediatric population.
4.Apoptotic activity of demethoxycurcumin in MG-63human osteosarcoma cells
Kyeong-Rok KANG ; Jae-Sung KIM ; Tae-Hyeon KIM ; Jeong-Yeon SEO ; Jong-Hyun PARK ; Hong Sung CHUN ; Sun-Kyoung YU ; Heung-Joong KIM ; Chun Sung KIM ; Do Kyung KIM
International Journal of Oral Biology 2021;46(1):23-29
Demethoxycurcumin (DMC), which is a curcuminoid found in turmeric, has anti-proliferative effects on cancer cells. However, the effect of DMC on osteosarcoma has not been established. The aim of this study was to examine the effects of DMC on cell growth and apoptosis induction in MG-63 human osteosarcoma cells. This study was investigated using 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromid assay, Live/Dead cell assay, 4’, 6-diamidino-2-phenylindole staining, and immunoblotting in MG-63 cells. DMC induced MG-63 cell death in a dosedependent manner, with an estimated IC50 value of 54.4 μM. DMC treatment resulted in nuclear condensation in MG-63 cells. DMC-induced apoptosis in MG-63 cells was mediated by the expression of Fas and activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting results showed that Bcl-2 and Bcl-xL were downregulated, while Bax and Bad were upregulated by DMC in MG-63 cells. These results indicated that DMC inhibits cell proliferation and induces apoptotic cell death in MG-63 human osteosarcoma cells via the death receptormediated extrinsic apoptotic pathway and mitochondria-mediated intrinsic apoptotic pathway.
5.Alpha-lipoic acid protects human dopaminergic neuronal cells against hydrogen peroxide-induced cell injury by inhibiting autophagy and apoptosis
Kyeong-Rok KANG ; Jae-Sung KIM ; Tae-Hyeon KIM ; Jeong-Yeon SEO ; HyangI LIM ; Jong-Hyun PARK ; Kwang Yeol YANG ; Sun-Kyoung YU ; Heung-Joong KIM ; Chun Sung KIM ; Hong Sung CHUN ; Dong-Seol LEE ; Joo-Cheol PARK ; Do Kyung KIM
International Journal of Oral Biology 2021;46(1):15-22
Alpha-lipoic acid (ALA) is a naturally occurring antioxidant and has been previously used to treat diabetes and cardiovascular disease. However, the autophagy effects of ALA against oxidative stress-induced dopaminergic neuronal cell injury remain unclear. The aim of this study was to investigate the role of ALA in autophagy and apoptosis against oxidative stress in the SH-SY5Y human dopaminergic neuronal cell line. We examined SH-SY5Y phenotypes using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay (cell viability/proliferation), 4′,6-diamidino-2-phenylindole dihydrochloride nuclear staining, Live/Dead cell assay, cellular reactive oxygen species (ROS) assay, immunoblotting, and immunocytochemistry. Our data showed ALA attenuated hydrogen peroxide (H2O2)-induced ROS generation and cell death. ALA effectively suppressed Bax up-regulation and Bcl-2 and BclxL down-regulation. Furthermore, ALA increased the expression of the antioxidant enzyme, heme oxygenase-1. Moreover, the expression of Beclin-1 and LC-3 autophagy biomarkers was decreased by ALA in our cell model. Combined, these data suggest ALA protects human dopaminergic neuronal cells against H2O2-induced cell injury by inhibiting autophagy and apoptosis.
6.The Role of Neurologists in Pain Management – Based on the Survey Conducted by the Korean Neurological Association in 2020
Kyomin CHOI ; Ohyun KWON ; Sang Beom KIM ; Yang-Ki MINN ; Kee Duk PARK ; Bum Chun SUH ; Jong-Geun SEO ; Eunhee SOHN ; Gun Sei OH ; Jeeyoung OH ; Kwang Soo LEE ; Dong Kuck LEE ; Jong-pil JEONG ; Soo Jin CHO ; Soohyun CHO ; Young Su HAN ; In Soo JOO
Journal of the Korean Neurological Association 2021;39(3):165-171
Background:
Pain is one of the most common chief complaints in neurological field. Authors try to inform the current situation of pain medicine in neurological practice and present an effective method for pain-related education during neurology residency and for practicing neurologists.
Methods:
A survey was conducted from November 16 to November 27, 2020 for members of the Korean Neurological Association, and the results were analyzed.
Results:
About two-thirds of neurologists replied that more than 25% of their patients were suffered from diverse pain including headache, spine pain or neuropathic pain. Despite many patients are visiting to neurologist for pain treatment, most neurologists are aware that they have not received sufficient practical pain education in the past and present. Therefore, they want more educational opportunities in pain medicine including interventional pain management and physical and pharmacologic therapies for more effective treatment.
Conclusions
More follow-up studies on pain treatment and education should be conducted. It is also essential that the members of the society continue to interest and participate in the change of the pain education program.
7.Postoperative Clinical Outcomes of Colonic Stent Placement as Bridge-to-surgery vs. Emergency Surgery in Left-sided Malignant Colonic Obstruction
Eun Ju CHOE ; Yong Kang LEE ; Han Ho JEON ; Jong Won CHOI ; Byung Kyu PARK ; Sun Young WON ; Jeong Hun SEO ; Chun Kyon LEE ; Yong Suk CHO
Journal of Digestive Cancer Report 2021;9(2):43-49
Background/Aims:
Colonic stenting as a bridge to elective surgery is an alternative for emergency surgery in patients with acute malignant colonic obstruction. However, since its benefits are uncertain, we aimed to establish whether it has better clinical outcomes.
Methods:
The patients with acute malignant left-sided colon obstruction enrolled from January 2009 to December 2018 in National Health Insurance Service Ilsan Hospital. The patients were enrolled to undergo colonic stenting as a bridge to elective surgery or emergency surgery. The following oncological outcomes were assessed: incidence of complete remission, disease progression, local recurrence, and systemic recurrence.
Results:
Out of 40 patients, 33 received self-expanding metallic stent (SEMS) as a bridge-tosurgery, and 7 underwent emergency surgery. More stoma was made in case of emergency surgery with statistical significance (p < 0.001). There were no significant differences in complete remission rate in curable left-sided malignant colonic obstruction between SEMS as a bridgeto-surgery and emergency surgery. Complete remission was achieved for 3 patients (42.9%) in the non-stent group and 27 patients (81.8%) in the stent group. There was no statistically significant difference in oncologic outcomes between the two groups (p = 0.069). According to multi-variate analysis, advanced TNM stage, Adjuvant chemotherapy, and SEMS bridge-tosurgery were significantly associated with disease-free survival. Disease-free survival rate differed significantly between the two groups (p = 0.024).
Conclusions
SEMS as a bridge-to-surgery might be an effective strategy and reduce stoma formation in acute malignant left-sided colon obstruction.
8.Experience of serious intestinal hemorrhage and perforation in small bowel lymphoma: a case report
Seo Ree KIM ; Sang Hoon CHUN ; Jong Youl JIN ; Tae-Geun GWEON ; Hayemin LEE ; Min-Sun JIN ; Guk Jin LEE
Korean Journal of Clinical Oncology 2021;17(2):126-130
There have been several reports of complications of small bowel lymphoma, such as bleeding, obstruction, and perforation, often require emergency surgery. It is hardly showed complications of bleeding and wound dehiscence for diffuse large B cell lymphoma with distal ileum involvement, which needed urgent surgery and medical management. A 65-year-old man with diffuse large B-cell lymphoma with distal ileum involvement experienced both intestinal bleeding and perforation during the course of treatment. As the patient was diagnosed with stage III disease, resection before chemotherapy was not considered due to the resulting delay in chemotherapy, which necessitated sufficient tissue healing. Chemotherapy is important when treating small bowel lymphoma, complications such as bleeding and perforation should always be considered for the treatment of small bowel lymphoma, and surgery is necessary in this situation. After surgery of the small bowel, subsequent chemotherapy could cause wound dehiscence and perforation; therefore, adequate recovery time should be given before chemotherapy.
9.Apoptotic activity of demethoxycurcumin in MG-63human osteosarcoma cells
Kyeong-Rok KANG ; Jae-Sung KIM ; Tae-Hyeon KIM ; Jeong-Yeon SEO ; Jong-Hyun PARK ; Hong Sung CHUN ; Sun-Kyoung YU ; Heung-Joong KIM ; Chun Sung KIM ; Do Kyung KIM
International Journal of Oral Biology 2021;46(1):23-29
Demethoxycurcumin (DMC), which is a curcuminoid found in turmeric, has anti-proliferative effects on cancer cells. However, the effect of DMC on osteosarcoma has not been established. The aim of this study was to examine the effects of DMC on cell growth and apoptosis induction in MG-63 human osteosarcoma cells. This study was investigated using 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromid assay, Live/Dead cell assay, 4’, 6-diamidino-2-phenylindole staining, and immunoblotting in MG-63 cells. DMC induced MG-63 cell death in a dosedependent manner, with an estimated IC50 value of 54.4 μM. DMC treatment resulted in nuclear condensation in MG-63 cells. DMC-induced apoptosis in MG-63 cells was mediated by the expression of Fas and activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting results showed that Bcl-2 and Bcl-xL were downregulated, while Bax and Bad were upregulated by DMC in MG-63 cells. These results indicated that DMC inhibits cell proliferation and induces apoptotic cell death in MG-63 human osteosarcoma cells via the death receptormediated extrinsic apoptotic pathway and mitochondria-mediated intrinsic apoptotic pathway.
10.Alpha-lipoic acid protects human dopaminergic neuronal cells against hydrogen peroxide-induced cell injury by inhibiting autophagy and apoptosis
Kyeong-Rok KANG ; Jae-Sung KIM ; Tae-Hyeon KIM ; Jeong-Yeon SEO ; HyangI LIM ; Jong-Hyun PARK ; Kwang Yeol YANG ; Sun-Kyoung YU ; Heung-Joong KIM ; Chun Sung KIM ; Hong Sung CHUN ; Dong-Seol LEE ; Joo-Cheol PARK ; Do Kyung KIM
International Journal of Oral Biology 2021;46(1):15-22
Alpha-lipoic acid (ALA) is a naturally occurring antioxidant and has been previously used to treat diabetes and cardiovascular disease. However, the autophagy effects of ALA against oxidative stress-induced dopaminergic neuronal cell injury remain unclear. The aim of this study was to investigate the role of ALA in autophagy and apoptosis against oxidative stress in the SH-SY5Y human dopaminergic neuronal cell line. We examined SH-SY5Y phenotypes using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay (cell viability/proliferation), 4′,6-diamidino-2-phenylindole dihydrochloride nuclear staining, Live/Dead cell assay, cellular reactive oxygen species (ROS) assay, immunoblotting, and immunocytochemistry. Our data showed ALA attenuated hydrogen peroxide (H2O2)-induced ROS generation and cell death. ALA effectively suppressed Bax up-regulation and Bcl-2 and BclxL down-regulation. Furthermore, ALA increased the expression of the antioxidant enzyme, heme oxygenase-1. Moreover, the expression of Beclin-1 and LC-3 autophagy biomarkers was decreased by ALA in our cell model. Combined, these data suggest ALA protects human dopaminergic neuronal cells against H2O2-induced cell injury by inhibiting autophagy and apoptosis.

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