• The Korean Journal of Physiology and Pharmacology
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• v.27 no.6
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• pp.521-531
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• 2023

Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (E_max) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.

• Journal of the Korean Society of Radiology
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• v.16 no.7
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• pp.1007-1014
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• 2022

Targeted radionuclide therapy (TRT) is a method of treating tumor cells using radiopharmaceuticals. Cells and nuclei constituting tissues of the human body are composed of spherical and oval shapes, but cancer cells are composed of various cell types. Therefore, this study analyzed the absorbed dose for each organelle according to the change in the size of the cell nucleus for beta-emitting nuclides during targeted radionuclide therapy through the Monte Carlo method. Cells were set in two sphere shapes, 5 ㎛ and 10 ㎛, and the internal structure was divided into cell nucleus, cytoplasm, and cell surface. Next, the absorbed dose according to the increase in the size of the cell nucleus was evaluated. As a result, ¹⁷⁷Lu among the target radionuclides showed the highest dose in all cell compartments. As the ratio of the nucleus in the cell increased, the absorbed dose on the cell surface increased, but the absorbed dose in the cytoplasm and nucleus tended to decrease. Accordingly, it is judged that it is important to select a radionuclide considering the size of cancer cells and determine an appropriate amount of radioactivity during targeted radionuclide treatment.

• Journal of Ginseng Research
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• v.48 no.1
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• pp.77-88
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• 2024

Background: Lung inflammation occurs in many lung diseases, but has limited effective therapeutics. Ginseng and its derivatives have anti-inflammatory effects, but their unstable physicochemical and metabolic properties hinder their application in the treatment. Panaxadiol (PD) is a stable saponin among ginsenosides. Inhalation administration may solve these issues, and the specific mechanism of action needs to be studied. Methods: A mouse model of lung inflammation induced by lipopolysaccharide (LPS), an in vitro macrophage inflammation model, and a coculture model of epithelial cells and macrophages were used to study the effects and mechanisms of inhalation delivery of PD. Pathology and molecular assessments were used to evaluate efficacy. Transcriptome sequencing was used to screen the mechanism and target. Finally, the efficacy and mechanism were verified in a human BALF cell model. Results: Inhaled PD reduced LPS-induced lung inflammation in mice in a dose-dependent manner, including inflammatory cell infiltration, lung tissue pathology, and inflammatory factor expression. Meanwhile, the dose of inhalation was much lower than that of intragastric administration under the same therapeutic effect, which may be related to its higher bioavailability and superior pharmacokinetic parameters. Using transcriptome analysis and verification by a coculture model of macrophage and epithelial cells, we found that PD may act by inhibiting TNFA/TNFAR and IL7/IL7R signaling to reduce macrophage inflammatory factor-induced epithelial apoptosis and promote proliferation. Conclusion: PD inhalation alleviates lung inflammation and pathology by inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells. PD may be a novel drug for the clinical treatment of lung inflammation.

• IMMUNE NETWORK
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• v.22 no.5
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• pp.40.1-40.24
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• 2022

Mesenchymal stem cells (MSCs) are attractive alternatives to conventional anti-asthmatic drugs for severe asthma. Mechanisms underlying the anti-asthmatic effects of MSCs have not yet been elucidated. This study evaluated the anti-asthmatic effects of intravenously administered MSCs, focusing on macrophages and monocytes. Seven-week-old transgenic (Tg) mice with lung-specific overexpression of IL-13 were used to simulate chronic asthma. MSCs were intravenously administered four days before sampling. We examined changes in immune cell subpopulations, gene expression, and histological phenotypes. IL-13 Tg mice exhibited diverse features of chronic asthma, including severe type 2 inflammation, airway fibrosis, and mucus metaplasia. Intravenous administration of MSCs attenuated these asthmatic features just four days after a single treatment. MSC treatment significantly reduced SiglecF^-CD11c^-CD11b⁺ monocyte-derived macrophages (MoMs) and inhibited the polarization of MoMs into M2 macrophages, especially M2a and M2c. Furthermore, MSCs downregulated the excessive accumulation of Ly6c^- monocytes in the lungs. While an intravenous adoptive transfer of Ly6c^- monocytes promoted the infiltration of MoM and Th2 inflammation, that of MSC-exposed Ly6c^- monocytes did not. Ex vivo Ly6c^- MoMs upregulated M2-related genes, which were reduced by MSC treatment. Molecules secreted by Ly6c^- MoMs from IL-13 Tg mice lungs upregulated the expression of fibrosis-related genes in fibroblasts, which were also suppressed by MSC treatment. In conclusion, intravenously administered MSCs attenuate asthma phenotypes of chronic asthma by modulating macrophages. Identifying M2 macrophage subtypes revealed that exposure to MSCs transforms the phenotype and function of macrophages. We suggest that Ly6c^- monocytes could be a therapeutic target for asthma management.

• Molecules and Cells
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• v.46 no.11
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• pp.688-699
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• 2023

We set up this study to understand the underlying mechanisms of reduced ceramides on immune cells in acute rejection (AR). The concentrations of ceramides and sphingomyelins were measured in the sera from hepatic transplant patients, skin graft mice and hepatocyte transplant mice by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Serum concentrations of C24 ceramide, C24:1 ceramide, C16:0 sphingomyelin, and C18:1 sphingomyelin were lower in liver transplantation (LT) recipients with than without AR. Comparisons with the results of LT patients with infection and cardiac transplant patients with cardiac allograft vasculopathy in humans and in mouse skin graft and hepatocyte transplant models suggested that the reduced C24 and C24:1 ceramides were specifically involved in AR. A ceramide synthase inhibitor, fumonisin B₁ exacerbated allogeneic immune responses in vitro and in vivo, and reduced tolerogenic dendritic cells (tDCs), while increased P3-like plasmacytoid DCs (pDCs) in the draining lymph nodes from allogeneic skin graft mice. The results of mixed lymphocyte reactions with ceranib-2, an inhibitor of ceramidase, and C24 ceramide also support that increasing ceramide concentrations could benefit transplant recipients with AR. The results suggest increasing ceramides as novel therapeutic target for AR, where reduced ceramides were associated with the changes in DC subsets, in particular tDCs.

• Journal of Life Science
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• v.34 no.3
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• pp.170-178
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• 2024

Adipose-derived stem cells (ADSCs) are capable of differentiation into multiple lineages of cells, which has attracted attention for clinical therapy. However, ADSCs have poor proliferation capacity and a short life span in culture, which is an impediment in the application to clinical use. Previously, to overcome growth disadvantages, we had established an immortalized ADSC line (ADSC-T) by introducing the SV40 T antigen coding gene into primary human ADSC. In the present study, we evaluated the differentiation potential of this cell line and assessed the anti-inflammatory effect of its conditioned medium (CM). ADSC-T appeared to maintain the differentiation potential into adipocyte and chondrocyte. The CM of ADSC-T suppressed the NF-κB activity and its target gene expression of COX-2 and iNOS. Furthermore, the phosphorylations of MAPKs, including ERK, JNK and p38, were suppressed by the ADSC-T CM. The expressions of pro-inflammatory cytokines such as TGF-β, TNF-α, IL-6, and IL-13 were also suppressed by the CM of ADSC-T. In the Nc/Nga atopic model mice, the CM showed therapeutic effect on DNCB-induced atopic dermatitis. These results indicate that the immortalized ADSC-T maintains the beneficial properties of primary ADSC and could be a versatile cell source for not only research into ADSC but also for production of CM suitable for clinical application.

• Journal of the Korean Society of Radiology
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• v.84 no.2
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• pp.418-426
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• 2023

Purpose Practical challenges are encountered in percutaneous intravascular procedures when applied to markedly angulated branching vessels. Herein, we introduced a folded-loop guidewire remodeling technique-the guidewire-shaping technique-to overcome difficult catheterization. Materials and Methods First, the tip of a 0.014-inch micro-guidewire was manually shaped like a pigtail loop. Second, the shaped guidewire was introduced into the microcatheter and was preloaded into the hollow metal introducer for suitability with the microcatheter hub. Gentle rotation of the guidewire after release from the microcatheter can create the preshaped pigtail loop configuration. On pulling back, the loop loosened, the configuration was changed to a small U-shaped tip, and the guidewire tip was easily introduced into the target artery. Results Between December 2019 and January 2022, the described technique was used in 64 patients (male/female, 49/15; mean age, 66.8 ± 9.5 years) for selective arterial embolization, after failed attempts with the conventional selection technique. The technique was successful in 63/64 patients (98%). The indications of embolization include transcatheter arterial chemoembolization, gastrointestinal bleeding, hemoptysis, trauma-induced bleeding, and tumor bleeding. Conclusion The folded-loop guidewire remodeling technique facilitates the catheterization of markedly angulated branching arteries; when usual catheterization method fails.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.16 no.2
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• pp.239-250
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• 2005

Objective : The purpose of this study was obtaining data on the efficacy and safety of risperidone in child and adolescent psychiatric patients. Method : Thirty one children and adolescents (males n=18, females n=13, age ranged from 5.4 to 17.3 years) treated with risperidone were selected among child and adolescent psychiatric inpatients of Seoul National University Hospital from January, 2001 to June, 2002, and charts for them were reviewed retrospectively. Results : The primary psychiatric disorders treated with risperidone were schizophrenia and other psychosis, bipolar I disorder with psychotic features, Tourette's disorder, autism spectrum disorders, mixed receptive and expressive language disorder, attention deficit-hyperactivity disorder, conduct disorder and obsessive-compulsive disorder. twelve of these had comorbid mental retardation. Primary target symptoms of risperidone were psychotic symptoms (n=13 or $41.9\%$), behavioral symptoms (n=10 or $32.3\%$) including aggression, impulsivity, hyperactivity, stereotypy nonresponsive to other psychiatric treatments, and chronic and severe tics (n=8, $25.8\%$). The efficacy of risperidone was measured by clinical global improvement (CGI) for target symptoms, $67.7\%$ of subjects showed moderate or marked improvements and its therapeutic effect appeared to be maintained during at least 7.5 months. Mean daily dosage of risperidone was $0.05{\pm}0.01mg/kg$, the group with psychotic symptoms had significantly higher mean daily dosage (0.07mg/kg) compared with other two groups (0.04mg/kg) with behavioral symptoms or tics. A variety of adverse events were reported in this study : weight gain (n=23) most commonly reported, extrapyramidal symptoms (n=15), autonomic symptoms (n=6), sedation (n=5) and symptoms related to hyperprolactinemia (n=2) etc. Although there was no drug change related to the adverse events of risperidone, and $90\%$ of subjects at their last visits were maintained on it, thus its tolerability appeared good. Conclusions Results suggest that risperidone may be relatively safe and effective drug in managing a wide variety of child and adolescent psychopathologies such as psychotic symptoms, behavioral symptoms including aggression, impulsivity, hyperactivity and stereotypy nonresponsive to other psychiatric treatments, and chronic and severe tics. Controlled and long-term studies of efficacy and safety of risperidone treatment for children and adolescents are recommended in the future.

• Progress in Medical Physics
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• v.20 no.2
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• pp.88-96
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• 2009

Radiation treatment for skin cancer has recently increased in tomotherapy. It was reported that required dose could be delivered with homogeneous dose distribution to the target without field matching using electron and photon beam. Therapeutic beam of tomotherapy, however, has several different physical characteristic and irradiation of helical beam is involved in the mechanically dynamic factors. Thus verification of skin dose is requisite using independent tools with additional verification method. Modified phantom for dose measurement was developed and skin dose verification was performed using inserted thermoluminescent dosimeters (TLDs) and GafChromic EBT films. As the homogeneous dose was delivered to the region including surface and 6 mm depth, measured dose using films showed about average 2% lower dose than calculated one in treatment planning system. Region indicating about 14% higher and lower absorbed dose was verified on measured dose distribution. Uniformity of dose distribution on films decreased as compared with that of calculated results. Dose variation affected by inhomogeneous material, Teflon, little showed. In regard to the measured dose and its distribution in tomotherapy, verification of skin dose through measurement is required before the radiation treatment for the target located at the curved surface or superficial depth.

• Journal of agricultural medicine and community health
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• v.12 no.1
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• pp.102-110
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• 1987

One of the familiar medical facility that most people reach easily in Korea is the drug store. In Korea, it is possible to purchase all kinds of common drugs without physician's prescriptions, which caused some problems. In other words, such treatment without professional supervision has led to medical, social and economical problems. In view of the above, this study is aimed at revealing the actual status of long-term use of drugs in some urban residents. Long-term use of drugs is operationally defined as using certain drugs at least once a week for more than 3 months. This survey took the residents of Guro 6-Dong where was one of the target areas for Community Health Development Project managed by Korea University as a target population. A sample of 1,517 residents was selected by the multistage sampling method. The interview was conducted on September 21st and 22nd in 1985. The object of this study was to compare the result with that of the rural area which was obtained by the same method, tools and research team, prior to this study in 1984. The results were as follows; 1) The age-standardization of the study showed that 97 per 1,000 urban residents were actually on long-term drug use. The prevalance of long-term use is high in accordance with aging and low with education level. 2) Out of 1,000 urban samples the most popular item involved in the long-term drug use was antipyretic-analgesic-antiinflammatory drug (26), and next in order was vitamin (23), antibiotics (13), digestives (10) and antacids (7). In the rural samples as for compare, that was antipyretic-analgesic-antiinflammatory drug (100), antacids (36), digestives (23), adrenocortical hormones (12) etc. 3) With antipyrctic-analgesic-antiinflammatory drugs, 50% of the urban samples were taking for more than a year, whereas such were 82.7% of the rural samples. Using such a high percentage of antipyretic-analgesic-antiinflamatory drugs in the rural residents is probably due to the high prevalence rate of musculo-skeletal diseases. 4) The urban long-term drug users of antipyretic-analgesic-antiinflammatory drugs were influenced mostly by the mass media (43.6%), next in order was pharmacist (35.9%) and physician (10.3%). Comparing with the result from the rural areas the role of mass media was much more influencial in the urban areas. 60% of them consulted with pharmacists, 14.3% with physicians and 25.7% had no history of consultation in the urban samples. 5) Considering the incidence of knowing the possible side-effects of each drug, 28.2% of the urban residents had no recognition about side-effects prior to use antipyretic-analgesic-antiinflammatory drugs. In the rural residents, 29.67o had no knowledge about the side-effects before using the drug. 6) For the solution of the above problems, it is necessary to limit the advertisement of some drugs by the parmaceutical company. And therapeutic drugs which may bring on side effects in case of long-term use should not be sold at drug stores without physician's prescription.