• Journal of Life Science
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• v.33 no.1
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• pp.102-113
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• 2023

This review discusses the cellular and molecular mechanisms by which the endometrial estrogen and progesterone receptors regulate local estrogen production, expression of the specific estrogen receptors, progesterone resistance, inflammatory responses and the differentiation and survival of endometriotic cells in endometrial inflammation. The epigenetic aberrations of endometrial stromal cells play an important role in the pathogenesis and progression of endometriosis. In particular, differential methylation of the estrogen receptor genes changes in the stromal cells the dominancy of estrogen receptor from ERα into ERβ, and results in the abnormal estrogen responses including inflammation, progesterone resistance and the disturbance of retinoid synthesis. These stromal cells also stimulate local estrogen production in response to PGE2 and the SF-1 mediated induction of steroidogenic enzyme expression, and the increased estradiol then feeds back into the ERβ to repeat the vicious inflammatory cycle through the activation of COX-2. In addition, high levels of ERβ expression may also change the chromatin structure of endometrial mesenchymal stem cells, and together with the repeated menstrual cycles can induce formation of the endometriotic tissue. The cascade of these serial events then leads to cell adhesion, angiogenesis and survival of the differentiation-disregulated stromal cells through the action of inflammatory factors such as ERβ-mediated estrogen, TNF-α and TGF-β1. Therefore, understanding of the dynamic hormonal changes during the menstrual cycle and the corresponding signal transduction mechanisms of the related nuclear receptors in endometrium would provide new insights for treating inflammatory diseases such as the endometriosis.

• Health Policy and Management
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• v.33 no.1
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• pp.3-18
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• 2023

Background: A chronic disease management program including patient education, recall and remind service, and reduction of out-of-pocket payment was implemented in Korea through a chronic care model. This study aimed to assess the effect of a community-based intervention program for improving medication adherence of patients with diabetes mellitus in rural areas of Korea. Methods: We applied a non-equivalent control group design using Korean National Health Insurance Big Data. Hongcheon County has been continuously adopting this program since 2012 as an intervention region. Hoengseong County did not adopt such program. It was used as a control region. Subjects were a cohort of patients with diabetes mellitus aged more than 65 years but less than 85 years among residents for 11 years from 2010 to 2020. After 1:1 matching, there were 368 subjects in the intervention region and 368 in the control region. Indirect indicators were analyzed using the difference-in-difference regression according to Andersen's medical use model. Results: The increasing percent point of diabetic patients who continuously received insurance benefits for more than 240 days from 2010 to 2014 and from 2010 to 2020 were 2.6%p and 2.7%p in the intervention region and 3.0%p and 3.9%p in the control region, respectively. The number of dispensations per prescription of diabetic patient in the intervention region increased by approximately 4.61% by month compared to that in the control region. Conclusion: The intervention program encouraged older people with diabetes mellitus to receive continuous care for overcoming the rule of halves in the community. More research is needed to determine whether further improvement in the continuity of comprehensive care can prevent the progression of cardiovascular diseases.

• Nutrition Research and Practice
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• v.17 no.5
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• pp.899-916
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• 2023

BACKGROUND/OBJECTIVES: Oxidative stress is a fundamental neurodegenerative disease trigger that damages and decimates nerve cells. Neurodegenerative diseases are chronic central nervous system disorders that progress and result from neuronal degradation and loss. Recent studies have extensively focused on neurodegenerative disease treatment and prevention using dietary compounds. Heseperetin is an aglycone hesperidin form with various physiological activities, such as anti-inflammation, antioxidant, and antitumor. However, few studies have considered hesperetin's neuroprotective effects and mechanisms; thus, our study investigated this in hydrogen peroxide (H₂O₂)-treated SH-SY5Y cells. MATERIALS/METHODS: SH-SY5Y cells were treated with H₂O₂ (400 µM) in hesperetin absence or presence (10-40 µM) for 24 h. Three-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability, and 4',6-diamidino-2-phenylindole staining allowed us to observe nuclear morphology changes such as chromatin condensation and apoptotic nuclei. Reactive oxygen species (ROS) detection assays measured intracellular ROS production; Griess reaction assays assessed nitric oxide (NO) production. Western blotting and quantitative polymerase chain reactions quantified corresponding mRNA and proteins. RESULTS: Subsequent experiments utilized various non-toxic hesperetin concentrations, establishing that hesperetin notably decreased intracellular ROS and NO production in H₂O₂-treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H₂O₂-induced inflammation-related gene expression, including interluekin-6, tumor necrosis factor-α, and nuclear factor kappa B (NF-κB) p65 activation. In addition, hesperetin inhibited NF-κB translocation into H₂O₂-treated SH-SY5Y cell nuclei and suppressed mitogen-activated protein kinase protein expression, an essential apoptotic cell death regulator. Various apoptosis hallmarks, including shrinkage and nuclear condensation in H₂O₂-treated cells, were suppressed dose-dependently. Additionally, hesperetin treatment down-regulated Bax/Bcl-2 expression ratios and activated AMP-activated protein kinase-mammalian target of rapamycin autophagy pathways. CONCLUSION: These results substantiate that hesperetin activates autophagy and inhibits apoptosis and inflammation. Hesperetin is a potentially potent dietary agent that reduces neurodegenerative disease onset, progression, and prevention.

• Journal of Life Science
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• v.34 no.6
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• pp.399-407
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• 2024

Angiogenesis is the process by which new blood vessels form from existing blood vessels. This phenomenon occurs during growth, healing, and menstrual cycle changes. Angiogenesis is a complex and multifaceted process that is important for the continued growth of primary tumors, metastasis promotion, the support of metastatic tumors, and cancer progression. Impaired angiogenesis can lead to cancer, autoimmune diseases, rheumatoid arthritis, cardiovascular disease, and delayed wound healing. Currently, there are only a handful of effective antiangiogenic drugs. Recent studies have shown that natural marine products exhibit antiangiogenic effects. In a previous study, we reported that the hexane extract of H. fusiformis (HFH) could inhibit the development of new blood vessels both in vitro and in vivo. The aim of this study was to describe the inhibitory effect of chloroform extracts of H. fusiformis on angiogenesis. To investigate how chloroform extract prevents blood vessel growth, we examined its effects on HUVEC, including cell migration, invasion, and tube formation. In a mouse Matrigel plug assay, H. fusiformis chloroform extract (HFC) also inhibited angiogenesis in vivo. Certain proteins associated with blood vessel growth were reduced after HFC treatment. These proteins include vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK)/extracellular signal transduction kinase, and serine/threonine kinase 1 (AKT). These studies have shown that the chloroform extract of H. fusiformis can inhibit blood vessel growth both in vitro and in vivo.

• The Journal of Internal Korean Medicine
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• v.45 no.2
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• pp.190-198
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• 2024

Introduction: Central pontine myelinolysis (CPM) is a rare neurological disorder marked by symmetric nerve fiber damage, commonly following rapid hyponatremia correction, with no established treatment and a poor prognosis. The condition, often linked to alcoholism, malnutrition, and various diseases, lacks comprehensive studies on its impact on gait. This research aims to quantitatively analyze gait changes in CPM patients receiving both traditional Korean and conventional rehabilitation treatments, addressing a gap in current understanding of CPM management. Case presentation: A 56-year-old male diagnosed with CPM following an initial misdiagnosis underwent combined electoracupuncture and rehabilitative treatment at ○○ university Korean medical center, resulting in significant gait improvements. A treadmill gait analysis system was used to measure changes in key gait parameters at 2-week intervals, and the patient's progress was documented. Conclusions: The quantitative analysis revealed significant gait improvements. Foot rotation decreased from 8.9° to 6.4° (right) and from 11.1° to 7.2° (left); lateral symmetry improved from -7.8 to 0.8; step length increased from 21 cm to 44 cm (right) and from 19 cm to 44 cm (left); and velocity increased from 1.2 m/s to 2.7 m/s. These findings highlight decreased foot rotation and lateral symmetry, along with increased step length and velocity, suggesting a positive outcome of the treatment regimen. Notably, the patient experienced no adverse effects related to the treatments. Despite limitations, including the singe case focus and lack of prior gait-focused CPM research, this case report provides valuable insights into effective CPM management strategies, paving the way for future research in this domain.

• Journal of Korean Neurosurgical Society
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• v.67 no.5
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• pp.510-520
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• 2024

Objective : Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The treatment of PD aims to alleviate motor symptoms by replacing the reduced endogenous dopamine. Currently, there are no disease-modifying agents for the treatment of PD. Zebrafish (Danio rerio) have emerged as an effective tool for new drug discovery and screening in the age of translational research. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to cause a similar loss of dopaminergic neurons in the human midbrain, with corresponding Parkinsonian symptoms. L-type calcium channels (LTCCs) have been implicated in the generation of mitochondrial oxidative stress, which underlies the pathogenesis of PD. Therefore, we investigated the neuro-restorative effect of LTCC inhibition in an MPTP-induced zebrafish PD model and suggested a possible drug candidate that might modify the progression of PD. Methods : All experiments were conducted using a line of transgenic zebrafish, Tg(dat:EGFP), in which green fluorescent protein (GFP) is expressed in dopaminergic neurons. The experimental groups were exposed to 500 μmol MPTP from 1 to 3 days post fertilization (dpf). The drug candidates : levodopa 1 mmol, nifedipine 10 μmol, nimodipine 3.5 μmol, diethylstilbestrol 0.3 μmol, luteolin 100 μmol, and calcitriol 0.25 μmol were exposed from 3 to 5 dpf. Locomotor activity was assessed by automated tracking and dopaminergic neurons were visualized in vivo by confocal microscopy. Results : Levodopa, nimodipine, diethylstilbestrol, and calcitriol had significant positive effects on the restoration of motor behavior, which was damaged by MPTP. Nimodipine and calcitriol have significant positive effects on the restoration of dopaminergic neurons, which were reduced by MPTP. Through locomotor analysis and dopaminergic neuron quantification, we identified the neuro-restorative effects of nimodipine and calcitriol in zebrafish MPTP-induced PD model. Conclusion : The present study identified the neuro-restorative effects of nimodipine and calcitriol in an MPTP-induced zebrafish model of PD. They restored dopaminergic neurons which were damaged due to the effects of MPTP and normalized the locomotor activity. LTCCs have potential pathological roles in neurodevelopmental and neurodegenerative disorders. Zebrafish are highly amenable to high-throughput drug screening and might, therefore, be a useful tool to work towards the identification of disease-modifying treatment for PD. Further studies including zebrafish genetic models to elucidate the mechanism of action of the disease-modifying candidate by investigating Ca2+ influx and mitochondrial function in dopaminergic neurons, are needed to reveal the pathogenesis of PD and develop disease-modifying treatments for PD.

• Tuberculosis and Respiratory Diseases
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• v.51 no.3
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• pp.240-247
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• 2001

Background : Tuberculous pleurisy treatments improve symptoms such as fever, chest pain, cough, and prevents the progression to active pulmonary tuberculosis and the development of residual pleural thickening that decrease diaphragm and rib cage movement This study investigated how the degree of residual pleural thickening affects the pulmonary function. Methods : Fifty seven patients who were initially diagnosed as having tuberculous pleurisy, were treated with anti-tuberculous medication for 6 months and had residual pleural thickening between May 1998 and January 2000 at the Eulji university hospital were reviewed. A chest X-ray and pulmonary function test(PFT, Sensormedics 2200) were performed. The predicted value(%) of the forced vital capacity(FVC), forced inspiratory vital capacity(FNC) and total lung capacity(TLC) were measured. The residual pleural thickening was defined the average of the summation in the lateral chest at the level of the imaginary line intersecting from the cardiophrenic angle to the diaphragmatic dome and the lowest part of the costophrenic angle between them. The results were sorted into three grades according to pleural thickness ; <2mm(grade I), 2~10mm(grade II), 10mm(grade III). Results : 1. FVC(% pred) and FIVC(% pred) were statistically different between grade I and III, and II and III. However, there was no difference between the TLC(% pred) between each of the groups. 2. The pleural thickness that cause restrictive dysfunction(FVC<80%) and a statistically difference, is 3mm. Conclusion : The larger the extent of the residual pleural thickness after antituberculous medication, the greater the reduction in the FVC, FIVC, TLC. A pleural thickness of 3mm is recommended as a guideline for diagnosing a restrictive pulmonary dysfunction.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.6
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• pp.1626-1632
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• 2008

Among patients who are receiving treatments at an oriental medical hospital for various symptoms and diseases, patients whose main disease is accompanied by metabolic syndrome with abnormal liver function. This research was performed in order to observe the progression of changes in the liver function and serum lipid profile after the oriental medical treatments to patients who have been receiving oriental medical treatment for various other diseases and have been diagnosed as having metabolic syndrome at their first visit to the hospital based on NCEP ATP III diagnosis criteria and WHO Asia Pacific region criteria. Total number of subject patients were 39cases(mean age:55.58${\pm}$2.09 years) which had 20 male and 19 female. For the references for hepatic enzyme levels and blood lipid profile were measured in before treatment and four times after treatments(every 2.31${\pm}$06.17 weeks). Serum AST was 48.86${\pm}$7.46 IU/L before oriental medical treatment. After the treatment, 40.63${\pm}$4.69, 43.12${\pm}$5.46, 37.82${\pm}$4.52 IU/L were measured where although the level decreased to the normal level compared to pre-treatment, the value was not significant statistically(P>0.05). ALT was 66.26${\pm}$11.01 IU/L before oriental medical treatment. After the treatment 62.10${\pm}$8.20, 61.10${\pm}$8.76, 43.79${\pm}$5.68 were measured where although the level decreased, abnormally high level was maintained. The last result was significant statistically(P<0.05) compared to pre-treatment. ALP was 193.06${\pm}$14.20 IU/L before oriental medical treatment. After the treatment, 176.80${\pm}$6.48, 177.46${\pm}$11.81, 162.41${\pm}$9.06 where although compared to pre-treatment the last result was significant statistically(P<0.05), the change was within the normal range. ${\gamma}$-GGT was 87.83${\pm}$12.59 IU/L before oriental medical treatment. After the treatment, progressively near normal level was achieved with 118.73${\pm}$46.45, 85.03${\pm}$17.12, 70.64${\pm}$10.93 and the last result was statistically significant compared to pre-treatment (P<0.05). Blood triglyceride was 217.63${\pm}$32.18 mg/dL before oriental medical treatment. After treatment 215.09${\pm}$22.18, 189.93${\pm}$22.44, 191.22${\pm}$18.51 where abnormal values continued even after treatment although results was not statistically significant compared to pre-treatment(P>0.05). Total-cholesterol was 197.28${\pm}$9.24 mg/dL before oriental medical treatment, after treatment 201.55${\pm}$11.13, 186.87${\pm}$8.77 and 186.68${\pm}$7.61 were measured that results were not statistically significant compared to pre-treatment(P>0.05). HDL-cholesterol was 41.88${\pm}$2.38 mg/dL before oriental medical treatment, after treatment 48.75${\pm}$4.22, 44.10${\pm}$1.91, 48.00${\pm}$2.06 the results were not statistically significant compared to pre-treatment(P>0.05). LDL-cholesterol was 111.66${\pm}$13.08 mg/dL before oriental medical treatment, after treatment 109.94${\pm}$10.18, 101.79${\pm}$8.63, 104.00${\pm}$6.98 the results were not statistically significant compared to pre-treatment(P>0.05). With such results, even if common oriental medical treatments were given to metabolic syndrome patients with abnormal liver function, the liver function was confirmed not to be aggravated, and the concentration of lipids in the blood was confirmed not to be affected in most patients.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.776-784
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• 1997

Background : Various combinations of treatment modalities have been reported in stage III non-small cell lung cancer (NSCLC). however, the standard treatment modality has not established yet. Recently, the efficacy of concurrent chemotherapy and radiation therapy has been reported in locally advanced lung cancer. We evaluate the response rate, toxicity, and survival of concurrent chemotherapy with etoposide and cisplatin(EP) and radiation therapy for unresectable stage III NSCLC. Method : Between October 1995 and December 1996, 32 patients with histologically proven unresectable stage III NSCLC without malignant pleural effusion were entered into this study. Twenty-nine patients were eligible for the response, survival, and toxicity analysis. Induction was two cycles of chemotherapy with etoposide and cisplatin plus concurrent chest RT to 4500cGy. Resection was attempted if the clinical response offered surgical resectability. Boost radiation therapy upto 5940cGy and one cycle of EP were performed if the disease were stable or responsive but still unresectable. Results : Of 29 eligible patients, 22(75.9%) showed partial response(PR). The progression free interval was 6.3months(range 1.1 to 19.5months). Surgical resection was performed in one patient. The median survival was 12.1months and one-year survival rate was 50.6%. The major toxicity was leukopenia($\geq$ grade 3, 46%). Thrombocytopenia over grade 3 was found in 11%. Radiation pneumonitis occurred in 13 patients(46%). Conclusion : Concurrent chemotherapy(EP) plus radiotherapy was effective and tolerable in the treatment of unresectable stage III NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.796-805
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• 1997

Background : It is clear that deregulation of cell cycle progression is a hallmark of neoplastic transformation and genes involved in the $G_1$/S transition of the cell cycle are especially frequent targets for mutations in human cancers, including lung cancer. p16 gene product, one of the G1 cell-cycle related proteins, that is recently identified plays an important role in the negative regulation of the the kinase activity of the cyclin dependent kinase (cdk) enzymes. Therefore p16 gene is known to be an important tumor suppressor gene and is also called MTS1 (multiple tumor suppressor 1). No more oncogenes have been reported to be frequently related to multiple different malignancies than the alterations of p16 gene. Especially when it comes to non-small cell lung cancer, there was no expression of p16 in more than 70% of cell lines examined. And also it is speculated that p16 gene could exert a key role in the development of non-small cell lung cancer. This study was designed to evaluate whether p16 gene could be used as a candidate for gene therapy of non-small cell lung cancer. Methods : After the extraction of total RNA from normal fibroblast cell line and subsequent reverse transcriptase reaction and polymerase chain reaction, the amplified p16 cDNA was subcloned into eukaryotic expression plasmid vector, pRC-CMV. The constructed pRC-CMV-p16 was transfected into the NCI-H441 NSCLC cell line using lipofectin. The changes of G1 cell-cycle related proteins were investigated with Western blot analysis and immunoprecipitation after extraction of proteins from cell lysates and tumor suppressive effect was observed by clonogenic assay. Results : (1) p16(-) NCI-H441 cell line transfected with pRC-CMV-p16 showed the formation of p16 : cdk 4 complex and decreased phosphorylated Rb protein, while control cell line did not. (2) Clonogenic assay demonstrated that the number of colony formation was markedly decreased in p16(-) NCI-H441 cell line transfected with pRC-CMV-p16 than the control cell line. Conclusion : It is confirmed that the expression of p16 protein in p16 absent NSCLC cell line with the gene transfection leads to p16 : cdk4 complex formation, subsequent decrease of phosphorylated pRb protein and ultimately tumor suppressive effects. And also it provides the foundation for the application of p16 gene as a important candidate for the gene therapy of NSCLC.