• Genomics & Informatics
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• v.11 no.4
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• pp.245-253
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• 2013

A radioresistant cell line was established by fractionated ionizing radiation (IR) and assessed by a clonogenic assay, flow cytometry, and Western blot analysis, as well as zymography and a wound healing assay. Microarray was performed to profile global expression and to search for differentially expressed genes (DEGs) in response to IR. H460R cells demonstrated increased cell scattering and acidic vesicular organelles compared with parental cells. Concomitantly, H460R cells showed characteristics of increased migration and matrix metalloproteinase activity. In addition, H460R cells were resistant to IR, exhibiting reduced expression levels of ionizing responsive proteins (p-p53 and ${\gamma}$-H2AX); apoptosis-related molecules, such as cleaved poly(ADP ribose) polymerase; and endoplasmic reticulum stress-related molecules, such as glucose-regulated protein (GRP78) and C/EBP-homologous protein compared with parental cells, whereas the expression of anti-apoptotic X-linked inhibitor of apoptosis protein was increased. Among DEGs, syntrophin beta 2 (SNTB2) significantly increased in H460R cells in response to IR. Knockdown of SNTB2 by siRNA was more sensitive than the control after IR exposure in H460, H460R, and H1299 cells. Our study suggests that H460R cells have differential properties, including cell morphology, potential for metastasis, and resistance to IR, compared with parental cells. In addition, SNTB2 may play an important role in radioresistance. H460R cells could be helpful in in vitro systems for elucidating the molecular mechanisms of and discovering drugs to overcome radioresistance in lung cancer therapy.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.2
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• pp.131-138
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• 2009

The binding of interleukin-6 (IL-6) cytokine family ligands to the gp130 receptor complex activates the Janus kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3) signal transduction pathway, where STA T3 plays an important role in cell survival and tumorigenesis. Constitutive activation of STAT3 has been frequently observed in many cancer tissues, and thus, blocking of the gp130 signaling pathway, at the JAK level, might be a useful therapeutic approach for the suppression of STAT3 activity, as anticancer therapy. AG490 is a tyrphostin tyrosine kinase inhibitor that has been extensively used for inhibiting JAK2 in vitro and in vivo. In this study, we demonstrate a novel mechanism associated with AG490 that inhibits the JAK/STAT3 pathway. AG490 induced downregulation of gp130, a common receptor for the IL-6 cytokine family compounds, but not JAK2 or STAT3, within three hours of exposure. The downregulation of gp130 was not caused by enhanced degradation of gp130 or by inhibition of mRNA transcription. It most likely occurred by translation inhibition of gp130 in association with phosphorylation of the eukaryotic initiation factor-2 a. The inhibition of protein synthesis of gp130 by AG490 led to immediate loss of mature gp130 in cell membranes, due to its short half-life, thereby resulting in reduction in the STAT3 response to IL-6. Taken together, these results suggest that AG490 blocks the STAT3 activation pathway via a novel pathway.

• Journal of Chest Surgery
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• v.29 no.12
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• pp.1381-1384
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• 1996

Thymoma Is an anterior mediastinal tumor, arising from the thymus, but occasionally has ectopic focus such as neck, trachea, thyroid, pulmonary hilum, lung parenchyme and pleura. Forty-two year old male patient was admitted due to progressive development of shortness of breath in 4 months. He had a history of exposure to asbestos for About 10 years duration In recent 15 years. Radiologically, multiple pleural masses were seen rom apex to diaphrAgm, with no evidence of anterior mediastinal mass,with fluid in right pleural cavity. Closed thoracotomy drainage with open biopsy were performed. Effusion cell block showed many T cell marker positive Lymphocytes & some epithelial cells compatible with thymoma, and the tissue also showed cortical type thymoma. Pleuropneumonectomy and thymectomy followed by 60 Gy radiation therapy were done and the patient is well 8 months postoperatively. The pleura is markedly thickened by the invasion of thymoma and the interstitial space of the lung tissue,but the normal appearance of thymus was present in remote area (Masaoka classification IVa). We report a case of ectopic invasive thymoma arising from the right pleura with intact thymus.

• Toxicological Research
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• v.33 no.4
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• pp.291-297
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• 2017

This study was performed to investigate the dose-response relationship between average daily cadmium dose (ADCD) from rice and the occurrence of urinary cadmium (U-Cd) in individuals eating that rice. This was a retrospective cohort designed to compare populations from two areas with different levels of cadmium contamination. Five-hundred and sixty-seven participants aged 18 years or older were interviewed to estimate their rice intake, and were assessed for U-Cd. The sources of consumed rice were sampled for cadmium measurement, from which the ADCD was estimated. Binary logistic regression was used to examine the association between ADCD and U-Cd (cut-off point at $2{\mu}g/g$ creatinine), and a correlation between them was established. The lowest estimate was $ADCD=0.5{\mu}g/kg\;bw/day$ [odds ratio (OR) = 1.71; with a 95% confidence interval (CI) 1.02-2.87]. For comparison, the relationship in the contaminated area is expressed by $ADCD=0.7{\mu}g/kg\;bw/day$, OR = 1.84; [95 % CI, 1.06-3.19], while no relationship was found in the non-contaminated area, meaning that the highest level at which this relationship does not exist is $ADCD=0.6{\mu}g/kg\;bw/day$ [95% CI, 0.99-2.95]. Rice, as a main staple food, is the most likely source of dietary cadmium. Abstaining from or limiting rice consumption, therefore, will increase the likelihood of maintaining U-Cd within the normal range. As the recommended maximum ADCD is not to exceed $0.6{\mu}g/kg\;bw/day$, the consumption of rice grown in cadmium-contaminated areas should not be more than 246.8 g/day. However, the exclusion of many edible plants grown in the contaminated area from the analysis might result in an estimated ADCD that does not reflect the true level of cadmium exposure among local people.

• Biomolecules & Therapeutics
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• v.17 no.2
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• pp.138-143
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• 2009

We have reported previously on a replication incompetent recombinant adenoviral vector, AdLPCD, in which the expression of cytosine deaminase gene (CD) is driven by the tumor-specific L-plastin promoter. AdLPCD vector had been evaluated for its efficacy of chemosensitization of ovarian cancer cells to 5-FC. In spite of the fact that ovarian cancer cells, i.e., OVCAR-3 and SK-OV-3, are capable for adenoviral transduction judged by LacZ reporter gene analysis, two cell lines demonstrated quite different sensitivities toward AdLPCD/5-FC system. In OVCAR-3 cells, infection of AdLPCD followed by exposure to 5-FC resulted in the suppression of cell growth with statistical significance. On the other hand, SK-OV-3 cells were more resistant to the CD/5-FC strategy compared with OVCAR-3 cells under the same condition. The object of study was to investigate factors that would determine the sensitivity to AdLPCD/5-FC. We evaluated conversion rate of 5-FC to 5-FU after infection of AdLPCD by HPLC analysis, $IC_{50}$ of 5-FU, the expression level of integrin receptors i.e., ${\alpha}v{\beta}3$ and ${\alpha}v{\beta}5$, and status of p53 in OVCAR-3 and SK-OV-3 cells. The results indicated that OVCAR-3 cells have few favorable features compared with SK-OV-3 cells to be more effective to the AdLPCD/5-FC strategy; higher level of ${\alpha}v{\beta}5$ integrin, higher rate of conversion of 5-FC into 5-FC, and lower $IC_{50}$ of 5-FU. The results suggest that the replacement of 5-FU with CD/5-FC in combination chemotherapy would be less toxic and much greater cytotoxicity than the conventional combination chemotherapy in some patients.

• Clinical and Experimental Pediatrics
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• v.64 no.2
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• pp.68-75
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• 2021

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading worldwide since December 2019. Hundreds of cases of children and adolescents with Kawasaki disease (KD)-like hyperinflammatory illness have been reported in Europe and the United States during the peak of the COVID-19 pandemic with or without shock and cardiac dysfunction. These patients tested positive for the polymerase chain reaction or antibody test for SARS-CoV-2 or had a history of recent exposure to COVID-19. Clinicians managing such patients coined new terms for this new illness, such as COVID-19-associated hyperinflammatory response syndrome, pediatric inflammatory multisystem syndrome temporally associated with COVID-19, or COVID-19-associated multisystem inflammatory syndrome in children (MIS-C). The pathogenesis of MIS-C is unclear; however, it appears similar to that of cytokine storm syndrome. MIS-C shows clinical features similar to KD, but differences between them exist with respect to age, sex, and racial distributions and proportions of patients with shock or cardiac dysfunction. Recommended treatments for MIS-C include intravenous immunoglobulin, corticosteroids, and inotropic or vasopressor support. For refractory patients, monoclonal antibody to interleukin-6 receptor (tocilizumab), interleukin-1 receptor antagonist (anakinra), or monoclonal antibody to tumor necrosis factor (infliximab) may be recommended. Patients with coronary aneurysms require aspirin or anticoagulant therapy. The prognosis of MIS-C seemed favorable without sequelae in most patients despite a reported mortality rate of approximately 1.5%.

• Journal of the Korean Society of Physical Medicine
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• v.13 no.4
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• pp.139-148
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• 2018

PURPOSE: This study compared the effects of indoor and outdoor environmental changes on the activity of the major lower limb muscles and walking factors in people 40-50 years and those aged older than 70 years. METHODS: Ten middle-aged people in their forties (age:$44.2{\pm}2.7$, BMI:$21.8{\pm}1.8$) and 10 elderly aged more than 70 years (age:$76.4{\pm}5.9$, BMI:$22.2{\pm}1.9$) with a normal walking ability were included. The participants walked 100 m both indoors and outdoors at their own speed. Using a 3D motion analyzer and EMG, the walking speed, angle of the ankle and activity changes of the lower limb muscles were compared. RESULTS: Significant differences in walking speed and peak-plantar flexion angle were observed between the two groups (p<.05). The muscular activity of the gastrocnemius muscle (GCM) was significantly different outdoors in the swing phase between the two groups (p<.05). In the people aged in their forties, the muscular activity of the rectus femoris (RF) was significantly higher outdoors than indoors (p<.05). In the elderly, however, the muscular activity of the RF was lower outdoors than indoors (p<.05). When compared to those in there forties, the muscular activity of the outdoor RF significantly decreased in the elderly group (P<.05). The muscular activity of the biceps femoris (BF) in the elderly decreased significantly outdoors compared to indoors (p<.05). CONCLUSION: For the elderly, increasing the exposure to the new environments or focusing on the performance of repeated movements for gradual speed control and precise movements is required to maintain normal gaits and movements that are less affected by environmental changes.

• Journal of Pharmacopuncture
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• v.22 no.2
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• pp.102-108
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• 2019

Objectives: Esophageal squamous cell carcinoma (ESCC) is considered as a deadly medical condition that affects a growing number of people worldwide. Targeted therapy of ESCC has been suggested recently and required extensive research. With cyclin D1 as a therapeutic target, the present study aimed at evaluating the anticancer effects of doxorubicin (Dox) or Hypericum perforatum L. (HP) extract encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles on the ESCC cell line KYSE30. Methods: Nanoparticles were prepared using double emulsion method. Cytotoxicity assay was carried out to measure the anti-proliferation activity of Dox-loaded (Dox NPs) and HP-loaded nanoparticles (HP NPs) against both cancer and normal cell lines. The mRNA gene expression of cyclin D1 was evaluated to validate the cytotoxicity studies at molecular level. Results: Free drugs and nanoparticles significantly inhibited KYSE30 cells by 55-73% and slightly affected normal cells up to 29%. The IC50 of Dox NPs and HP NPs was ~ 0.04-0.06 mg/mL and ~ 0.6-0.7 mg/mL, respectively. Significant decrease occurred in cyclin D1 expression by Dox NPs and HP NPs (P < 0.05). Exposure of KYSE-30 cells to combined treatments including both Dox and HP extract significantly increased the level of cyclin D1 expression as compared to those with individual treatments (P < 0.05). Conclusion: Dox NPs and HP NPs can successfully and specifically target ESCC cells through downregulation of cyclin D1. The simultaneous use of Dox and HP extract should be avoided for the treatment of ESCC.

• The Korean Journal of Pain
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• v.34 no.3
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• pp.304-314
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• 2021

Background: The study investigated virtual reality (VR) immersion in alleviating procedure-related pain in patients with chronic pain undergoing fluoroscopy-guided minimally-invasive intervention in a prone position at an outpatient clinic. Methods: In this prospective randomized controlled study, 38 patients undergoing lumbar sympathetic ganglion block were randomized into either the VR or the control group. In the VR group, procedure-related pain was controlled via infiltration of local anesthetics while watching a 30-minute VR hypnotic program. In the control group, the skin infiltration alone was used, with the VR device switched off. The primary endpoint was an 11-point score on the numerical rating scale, indicating procedure-related pain. Patients' satisfaction with pain control, anxiety levels, the need for additional local anesthetics during the procedure, hemodynamic stability, and any adverse events were assessed. Results: Procedure-related pain was significantly lower in the VR group (3.7 ± 1.4) than in the control group (5.5 ± 1.7; P = 0.002). Post-procedural anxiety was lower in the VR group than in the control group (P = 0.025), with a significant reduction from pre-procedural anxiety (P < 0.001). Although patients' satisfaction did not differ significantly (P = 0.158) between the groups, a higher number of patients required additional local anesthetics in the control group (n = 13) than in the VR group (n = 4; P = 0.001). No severe adverse events occurred in either group during the study. Conclusions: VR immersion can be safely used as a novel adjunct to reduce procedural pain and anxiety during fluoroscopic pain intervention.

• Journal of Veterinary Clinics
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• v.39 no.3
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• pp.131-137
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• 2022

Osteomyelitis typically occurs because of the direct inoculation of bacteria or fungi after penetrating trauma or surgical contamination or, by extension, from soft tissue infection. Osteomyelitis is rarely reported in wildlife animals, though severe chronic osteomyelitis cases do exist in wildlife owing to the scarcity of medical support in the wild environment. This report describes three cases of chronic osteomyelitis in wild raccoon dogs related to trauma. The typical symptoms of three reported cases were ataxia, stiffness, muscle atrophy, and lethargy. All three cases were relevant to traumatic or severe external injury, and skin infestation caused by ectoparasites was apparent on an ocular inspection. In the radiographic examination, diffuse sites of osteolytic lesions and remarkable periosteal responses were demonstrated around the injured limb in all three cases. Apparent neutrophilia with a left shift, lymphocytosis, and monocytosis in hematological examinations generally indicated chronic infection as shown in case 1 and 3. Treatment was attempted with broad-spectrum antibiotics and non-steroidal anti-inflammatory drugs, such as amoxicillin/clavulanic acid, enrofloxacin, clindamycin, and meloxicam. These treatment options helped improve the overall prognosis of chronic osteomyelitis, but the outcomes did not meet the treatment goal entirely. Osteomyelitis can be extremely challenging to treat, particularly in wild animals, because of their distinctive traits, such as masking phenomenon and uncontrolled exposure to ectoparasites. Earlier diagnosis with a radiographic examination, hematological examinations, and careful patient monitoring, followed by prolonged antibiotic therapy and restricted exercise, are the key factors leading to a better prognosis.