• Journal of Pharmacopuncture
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• v.25 no.4
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• pp.390-395
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• 2022

Objectives: Sweet bee venom (sBV) is purified from Apis mellifera, containing a high level of melittin-its main component. It has been used as a therapeutic agent for pain relief and anti-inflammation, as well as for treating neuronal abnormalities. Recently, there have been studies on the therapeutic application of sBV for anticancer treatment. In the present study, we investigated the pharmacological effect of sBV treatment in A549 human lung cancer cells. Methods: We used microscopic analysis to observe the morphological changes in A549 cells after sBV treatment. The MTT assay was used to examine the cytotoxic effect after dose-dependent sBV treatment. Molecular changes in sBV were evaluated by the expression of apoptosis marker proteins using western blot analysis. Results: Microscopic analysis suggested that the growth inhibitory effect occurred in a dose-dependent manner; however, cell lysis occurred at a concentration over 20 ㎍/mL of sBV. The MTT assay indicated that sBV treatment exhibited a growth inhibitory effect at a concentration over 5 ㎍/mL. On fluorescence activated cell sorting analysis, G0 dead cells were observed after G1 arrest at treatment concentrations up to 10 ㎍/mL. However, rapid cell rupture was observed at a concentration of 20 ㎍/mL. Western blot analysis demonstrated that sBV treatment modulated the expression of multiple cell death-related proteins, including cleaved-PARP, cleaved-caspase 9, p53, Bcl2, and Bax. Conclusion: sBV induced cell death in A549 human lung cancer cells at a pharmacological concentration, albeit causing hemolytic cell death at a high concentration.

• Journal of dental hygiene science
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• v.23 no.2
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• pp.169-175
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• 2023

Background: Although microbial infection is direct cause of periodontal disease, various environmental factors influence the disease severity. Aging is considered a risk factor for oral diseases, with the prevalence of periodontal diseases increasing with age. Moreover, senescence-associated secretory phenotype (SASP) expressed in age-related diseases is a key marker of chronic inflammation and aging phenotypes. Therefore, this study aimed to understand the relevance of senescent cells to periodontal health and disease, investigate the possibility of regulating the expression of aging- and osteolysis-related factors in gingival fibroblasts, and investigate the effect of senescence induction in gingival fibroblasts on osteoclast differentiation in mouse bone marrow-derived macrophages (BMMs). Methods: After stimulation with 400 nM hydrogen peroxidase, human gingival fibroblasts (HGFs) were examined for senescence-associated β-galactosidase. Western blot and enzyme-linked immunosorbent assays were performed to assess the expression of SASP. Osteoclast formation was assessed in BMMs using a conditioned medium (CM) from hydrogen peroxide-stimulated HGFs. Osteoclastic differentiation was investigated using tartrate-resistant acid phosphatase (TRAP) staining and activity. Data analysis was performed using SPSS version 25.0. Results: The expression of senescence-related molecules, including p53, p16, and p21, and the expression of osteolytic factors, including IL-6, IL-8, and IL-17, were found to be significantly higher in the hydrogen peroxide-stimulated HGF than in the control group. Regarding the indirect effects of senescent gingival cells, the number of osteoclasts and TRAP activity increased according to the differentiation of BMM cultured in CM. Conclusion: Our results on the of between osteolytic factors and cellular senescence in gingival fibroblast cells helped to reveal evidence of pathological aging mechanisms. Furthermore, our results suggest that the development of novel therapies that target specific SASP factors could be an effective treatment strategy for periodontal disease.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2022.09a
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• pp.103-103
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• 2022

Ganghwaljetongyeum (GHJTY) is a complex herbal decoction comprising 18 plants; it is used to treat arthritis. In order to develop a new anti-arthritic herbal medication, we selected 5 out of 18 GHJTY plants by using bioinformatics analysis. The new medication, called ChondroT, comprised water extracts of Osterici Radix, Lonicerae Folium, Angelicae Gigantis Radix, Clematidis Radix, and Phellodendri Cortex. This study was designed to investigate its chondroprotective and anti-inflammatory effects to develop an anti-arthritic herb medicine. ChondroT was validated using a convenient and accurate high-performance liquid chromatography. photodiode array (HPLC-PDA) detection method for simultaneous determination of its seven reference components. The concentrations of the seven marker constituents were in the range of 0.81-5.46 mg/g. The chondroprotective effects were evaluated based on SW1353 chondrocytes and matrix metalloproteinase 1 (MMP1) expression. In addition, the anti-inflammatory effects of ChondroT were studied by Western blotting of pro-inflammatory enzymes and by enzyme-linked immunosorbent assay (ELISA) of inflammatory mediators in lipopolysaccharides (LPS)-induced RAW264.7 cells. ChondroT enhanced the growth of SW1353 chondrocytes and also significantly inhibited IL-1β-induced MMP-1 expression. However, ChondroT did not show any effects on the growth of HeLa and RAW264.7 cells. The expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was induced by LPS in RAW264.7 cells, which was significantly decreased by pre-treatment with ChondroT. In addition, ChondroT reduced the activation of NF-κB and production of inflammatory mediators, such as IL-1β, IL-6, PGE2, and nitric oxide (NO) in LPS-induced RAW264.7 cells. These results show that ChondroT exerted a chondroprotective effect and demonstrated multi-target mechanisms related to inflammation and arthritis. In addition, the suppressive effect was greater than that exhibited by GHJTY, suggesting that ChondroT, a new complex herbal medication, has therapeutic potential for the treatment of arthritis.

• Korean Journal of Radiology
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• v.22 no.10
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• pp.1671-1679
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• 2021

Objective: We quantitatively measured the fat fraction (FF) in the vertebrae of patients with ankylosing spondylitis (AS) using magnetic resonance imaging (MRI) and investigated the role of FF as an indicator of both active inflammation and chronicity. Materials and Methods: A total of 52 patients with AS who underwent spinal MRI were retrospectively evaluated. The FF values of the anterosuperior and anteroinferior corners of the bone marrow in the L1-S1 spine were assessed using the modified Dixon technique. AS activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), AS Disease Activity Score (ASDAS), and serum inflammatory marker levels. AS disease chronicity was assessed by AS disease duration and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Univariable and multivariable regression analyses were conducted to investigate the correlation between FF and other clinical characteristics. Results: The mean FF ± standard deviation of the total lumbar spine was 43.0% ± 11.3%. At univariable analysis, spinal FF showed significant negative correlation with BASDAI (β = -0.474, p = 0.002) and ASDAS with C-reactive protein (ASDAS-CRP; β = -0.478, p = 0.002) and a significant positive correlation with AS disease duration (β = 0.440, p = 0.001). After adjusting for patient age, sex, and total mSASSS score, spinal FF remained significantly negatively correlated with BASDAI (β = -0.543, p < 0.001), ASDAS-CRP (β = -0.568, p < 0.001), and ASDAS with erythrocyte sedimentation rate (β = -0.533, p = 0.001). Spinal FF was significantly lower in patients with very high disease activity (ASDAS-CRP > 3.5) than in those with only high disease activity (2.1 ≤ ASDAS-CRP ≤ 3.5) (p = 0.010). Conclusion: Spinal FF may help assess both AS disease activity and chronicity.

• Journal of Convergence Korean Medicine
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• v.6 no.1
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• pp.29-36
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• 2024

Objectives: Psoriasis is a common chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and an excessive inflammatory response. Agents that can attenuate keratinocyte hyperproliferation and excessive inflammatory responses are considered potentially useful for the treatment of psoriasis. Daehwangmokdanpitang (DHMDPT) exhibits a broad range of bioactivities, including anti-proliferative and anti-inflammatory effects. This study aims to evaluate the anti-psoriatic potential of DHMDPT in vitro. Methods: HaCaT keratinocytes were stimulated with a mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) to establish an in vitro psoriatic keratinocyte model. Cell viability was measured using the MTT assay. Quantitative real-time PCR (qRT-PCR) was performed to measure the mRNA levels of the hyperproliferative marker gene keratin 6 (KRT6) and inflammatory factors such as IL-6, TNF-α, and IL-23A. Additionally, chemokines including CCL5, CCL2, CCL20, and CXCL1 were measured by qRT-PCR. Results: DHMDPT attenuated M5-induced hyperproliferation, as indicated by a reduction in KRT6 expression in HaCaT keratinocytes. M5 stimulation significantly upregulated the mRNA levels of IL-6, TNF-α, and IL-23A. However, DHMDPT treatment attenuated the upregulation of IL-6 but not TNF-α or IL-23A. Additionally, DHMDPT inhibited the expression of CCL5, CCL2, and CXCL1, but not CCL20. Conclusion: DHMDPT effectively attenuated the M5-induced proliferation and inflammatory response in HaCaT keratinocytes. Therefore, DHMDPT could be an attractive candidate for future development as an anti-psoriatic agent.

• Journal of Animal Reproduction and Biotechnology
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• v.39 no.2
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• pp.145-152
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• 2024

Background: Despite its anticancer activity, cisplatin exhibits severe testicular toxicity when used in chemotherapy. Owing to its wide application in cancer therapy, the reduction of damage to normal tissue is of imminent clinical need. In this study, we evaluated the effects of catechin hydrate, a natural flavon-3-ol phytochemical, on cisplatin-induced testicular injury. Methods: Type 2 mouse spermatogonia (GC-1 spg cells) were treated with 0-100 μM catechin and cisplatin. Cell survival was estimated using a cell proliferation assay and Ki-67 immunostaining. Apoptosis was assessed via flow cytometry with the Dead Cell Apoptosis assay. To determine the antioxidant effects of catechin hydrate, Nrf2 expression was measured using qPCR and CellROX staining. The anti-inflammatory effects were evaluated by analyzing the gene and protein expression levels of iNOS and COX2 using qPCR and immunoblotting. Results: The 100 μM catechin hydrate treatment did not affect healthy GC-1 spg cells but, prevented cisplatin-induced GC-1 spg cell death via the regulation of anti-oxidants and inflammation-related molecules. In addition, the number of apoptotic cells, cleaved-caspase 3 level, and BAX gene expression levels were significantly reduced by catechin hydrate treatment in a cisplatin-induced GC-1 spg cell death model. In addition, antioxidant and anti-inflammatory marker genes, including Nrf2, iNOS, and COX2 were significantly downregulated by catechin hydrate treatment in cisplatintreated GC-1 cells. Conclusions: Our study contributes to the opportunity to reintroduce cisplatin into systemic anticancer treatment, with reduced testicular toxicity and restored fertility.

• Herbal Formula Science
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• v.32 no.3
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• pp.263-275
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• 2024

Background : Recent studies have shown that stress fundamentally influences the functional modulation of organ and stress-related disease causes high morbidity and mortality rates. Objective : The present research investigated the effect of restraint stress on psychological and physiological responses. Results : Body weight and food intake were changed in stress group. Body weight has continuously decreased, and food intake has been slightly altered. As a result of measuring each tissue's weight, the liver and kidney's weight loss was greater than that of other organs. The lipid profile of stressed animals showed significant increases in cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels compared to control. As hepatic marker enzymes, serum glutamic pyruvic transaminase (GPT; alanine aminotransferase), glutamic oxalacetic transaminase (GOT; aspartate aminotransferase), and lactic dehydrogenase (LDH) were increased in the stress group. However, levels of serum cortisol and corticosterone did not affect. Results of the behavioral tests show that the stress group has increased activity, sluggish movements, and anxiety in the central part compared with the control group through the open field test. In the forced swim test, the stress group models had a longer duration of slowing movement, and its rate also increased. Also, in immunoblotting, stress increased the inflammatory factors Inducible Nitric Oxide Synthase (iNOS), cyclooxygenase-2 (COX-2) and activated the mitogen-activated protein kinase (MAPK) pathway. Conclusions : We observed that mouse model were affected behavioral response and liver injury when exposed to restraint stress, indicating the importance of the restraint stress in the development of psychological and physiological processes.

• Tuberculosis and Respiratory Diseases
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• v.61 no.4
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• pp.330-338
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• 2006

Background: The main factors associated with weight loss in patients with COPD are not well known. Since chronic inflammation and oxidative stress play a major pathogenic role in COPD, these factors may be responsible for the patients' weight loss. Therefore, this study measured the body mass index (BMI) in COPD patients and evaluated the variables, such as systemic inflammatory marker, oxidative stress and lung function, that correlate with the BMI. Method: The stable COPD patients (M:F=49:4, mean age=$68.25{\pm}6.32$) were divided into the lower (<18.5), normal (18.5-25) and higher (>25) BMI group. The severity of the airway obstruction was evaluated by measuring the $FEV_1$. The serum IL-6 and TNF-$\alpha$ levels were measured to determine the degree of systemic inflammation, and the carbonyl protein and 8-iso-prostaglandin $F_2{\alpha}$ level was measured to determine the level of oxidative stress. Each value in the COPD patients and normal control was compared with the BMI. Results: 1) Serum 8-iso-prostaglandin $F_2{\alpha}$ in COPD patients was significantly higher ($456.08{\pm}574.12pg/ml$) than that in normal control ($264.74{\pm}143.15pg/ml$) (p<0.05). However, there were no significant differences in the serum IL-6, TNF-$\alpha$, carbonyl protein between the COPD patients and normal controls. 2). In the COPD patients, the $FEV_1$ of the lower BMI group was significantly lower ($0.93{\pm}0.25L$) than that of the normal BMI ($1.34{\pm}0.52L$) and higher BMI groups ($1.72{\pm}0.41L$) (p<0.05). The lower $FEV_1$ was significantly associated with a lower BMI in COPD patients (p=0.002, r=0.42). The BMI of very severe COPD patients was significantly lower ($19.8{\pm}2.57$) than that of the patients with moderate COPD ($22.6{\pm}3.14$) (p<0.05). 3). There were no significant differences in the serum IL-6, TNF-$\alpha$, carbonyl protein and 8-iso-prostaglandin $F_2{\alpha}$ according to the BMI in the COPD patients. Conclusion: The severity of the airway obstruction, not the systemic inflammatory markers and oxidative stress, might be associated with the BMI in stable COPD patients. Further study will be needed to determine the factors associated with the decrease in the BMI of COPD patients.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.922-931
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• 2000

Background : It has been well known that bronchia1 asthma is a chronic airway inflammatory disorder. Recently, sputum induced with hypertonic saline was introduced as a simple and useful nonivasive medium to investigate airway inflammation and symptom severity in patients with asthma. We examined the eosinophil, eosinophil cationic protein (ECP), interleukin(IL)-3, IL-5, granulocyte-macrophage colony-stimulating facta (GM-CSF), and nitric oxide (NO) derivatives in induced sputum from patients with bronchia1 asthma in order to determine the role of NO and various inflammatory cytokines as a useful markers of airway inflammation or changes in pulmonary function tests and symptoms. Methods : A total 30 patients with bronchia1 asthma received oral prednisolone 30 mg daily for 2 weeks. Forced expiratory volume in one second ($FEV_1$), total blood eosinophil count and induced sputum eosinophil count, ECP, IL-3, IL-5, GM-CSF, and NO derivatives were determined before and after the administration of prednisolone. Results : Of the 30 patients, 13 (43.3%) were male and 17 (56.7%) were female. The mean age of patients was 41.8 years (range 19-64 years). Two patients could not produce sputum at the second study and 3 could not be followed up after their first visit. Two weeks after the prednisolone administration, there was a significant increase in $FEV_1$ (% of predicted value) from 78.1$\pm$20.6 % to 90.3$\pm$ 18.3 % (P<0.001). The eosinophil percentages in induced sputum were significantly decreased after treatment with prednisolone, with values of 56.1$\pm$27.2 % versus 29.6$\pm$21.3 % (P<0.001), and ECP were $134.5\pm68.1\;{\mu}g/L$ versus $41.5\pm42.4\;{\mu}g/L$ (P<0.001) respectively. After the prednisolone treatments, the eotaxin concentration also showed a decreasing tendency from 26.7$\pm$12.8 pg/ml to 21.7$\pm$8.7 pg/ml. There was a decreasing tendency but no significant differences in total blood eosinophil count (425.7$\pm$265.9 vs 287.7$\pm$294.7) and in the concentration of NO derivatives ($70.4\pm44.6{\mu}mol/L$ vs $91.5\pm48.3\;{\mu}mol/L$) after the prednisolone treatments. IL-3, IL-5, GM-CSF were undetectable in the sputum of most subjects either before the prednisolone treatments or after the treatments. Before the prednisolone treatments, a significant inverse correlation was observed between FEV1 and sputum ECP (r=-D.364, P<0.05) and there was a significant correlation between sputum eosinophils and eotaxin (r=0.369, P<0.05) Conclusion : The eotaxin and ECP concentration in induced sputum may be used as markers of airway inflammation after treatments in bronchia1 asthma. In addition, the measurement of sputum eosinophil percent ages is believed to be a simple method displaying the degree of airway inflammation and airway obstruction before and after the prednisolone treatment in bronchia1 asthma. However, unlike exhaled NO, the examination of NO derivatives with Griess reaction in induced sputum is considered an ineffective marker of changing airway inflammation and obstructing symptoms.

• Korean Journal of Psychosomatic Medicine
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• v.31 no.2
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• pp.165-172
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• 2023

Objectives : The purpose of this study is to determine whether there is a significant difference in the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio according to the history of suicide attempt in patients with psychiatric diseases. Methods : A medical record review was conducted on patients who had been hospitalized in Konyang University Hospital since 2021-03-01 to 2023-02-28 to collect demographic and clinical characteristics. T-test for continuous variables and Chi-square test for categorical variables were performed to determine demographic differences according to the history of suicide attempt, and the ANCOVA test was performed to compare the average value of peripheral inflammatory marker according to the history of suicide attempt with gender and age as covariates. One-way variance analysis was performed to determine whether the number of suicide attempt causes significant difference of the peripheral inflammatory marker. Results : The final analysis target of this study was 266 patients, 101 had history of suicide attempt, and 165 had no history of suicide attempt. The neutrophil-to-lymphocyte ratio (p<0.001) and platelet-to-lymphocyte ratio (p<0.001) were higher in patients with the history of suicide attempt than patients without the history of suicide attempt, but the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were not significantly increased depending on the serial increase of number of suicide attempts. Conclusions : This study suggests that peripheral inflammatory markers are meaningful and easily accessible indicators for predicting the risk of suicide attempt in psychiatric patients. We expect that prospective follow-up study will be conducted with more subjects and controlled potential confounding variables.