• 동의생리병리학회지
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• 제20권1호
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• pp.37-42
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• 2006

Matrix metalloproteinase-9 (MMP-9) is considered to be an important component in the progression of inflammation. Monocytes/macrophages are prominent at inflammation sites, and activation of these cells by stimulants such as lipopolysaccharide (LPS) leads to the production of significant amounts of MMP-9. Here, we show that LPS-induced MMP-9 production and activation was inhibited by the water extract from the fruit of Chaenomeles sinensis (CS), the root of Polygonum cuspidatum (PC), but increased by the extract from Boswellia carterii (BC). To investigate the mechanism by which those extracts inhibits MMP-9 activation, we examined the level of MMP-9 mRNA expression. We observed a significant change in the MMP-9 expression between LPS alone and LPS plus Chaenomeles sinensis and Polygonum cuspidatum extracts-treated cells. In addition, LPS significantly up-regulated MMP-9 promoter activity in Raw 264.7 cells, which was attenuated by the CS and PS extracts. However, water extracts from Boswellia carterii increased MMP-9 expression and MMP-9 promoter activity which were induced by LPS treatment in Raw 264.7 cells. These data suggest that water extracts from Chaenomeles sinensis and Polygonum cuspidatum can modulate anti-inflammatory immune response, which may be in part associated with the regulation of MMP-9 production and/or activation through the regulation of MMP-9 expression in mouse macrophage cells.

• Toxicological Research
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• 제27권4호
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• pp.253-259
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• 2011

Transforming growth factor ${\beta}$ (TGF-${\beta}$) is involved in cellular processes including growth, differentiation, apoptosis, migration, and homeostasis. Generally, TGF-${\beta}$ is the inhibitor of cell cycle progression and plays a role in enhancing the antagonistic effects of many growth factors. Unlike the antiproliferative effect of TGF-${\beta}$, E2, an endogeneous estrogen, is stimulating cell proliferation in the estrogen-dependent organs, which are mediated via the estrogen receptors, $ER{\alpha}$ and $ER{\beta}$, and may be considered as a critical risk factor in tumorigenesis of hormone-responsive cancers. Previous researches reported the cross-talk between estrogen/$ER{\alpha}$ and TGF-${\beta}$ pathway. Especially, based on the E2-mediated inhibition of TGF-${\beta}$ signaling, we examined the inhibition effect of 4-tert-octylphenol (OP) and 4-nonylphenol (NP), which are well known xenoestrogens in endocrine disrupting chemicals (EDCs), on TGF-${\beta}$ signaling via semi-quantitative reverse-transcription PCR. The treatment of E2, OP, or NP resulted in the downregulation of TGF-${\beta}$ receptor2 (TGF-${\beta}$ R2) in TGF-${\beta}$ signaling pathway. However, the expression level of TGF-${\beta}1$ and TGF-${\beta}$ receptor1 (TGF-${\beta}$ R1) genes was not altered. On the other hand, E2, OP, or NP upregulated the expression of a cell-cycle regulating gene, c-myc, which is a oncogene and a downstream target gene of TGF-${\beta}$ signaling pathway. As a result of downregulation of TGF-${\beta}$ R2 and the upregulation of c-myc, E2, OP, or NP increased cell proliferation of BG-1 ovarian cancer cells. Taken together, these results suggest that E2 and these two EDCs may mediate cancer cell proliferation by inhibiting TGF-${\beta}$ signaling via the downregulation of TGF-${\beta}$ R2 and the upregulation of c-myc oncogene. In addition, it can be inferred that these EDCs have the possibility of tumorigenesis in estrogen-responsive organs by certainly representing estrogenic effect in inhibiting TGF-${\beta}$ signaling.

• Journal of Breast Cancer
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• 제21권4호
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• pp.371-381
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• 2018

Purpose: Immune suppression is common in patients with advanced breast cancer but the mechanisms underlying this phenomenon have not been sufficiently studied. In this study, we aimed to identify B7 family members that were able to predict the immune status of patients, and which may serve as potential targets for the treatment of breast cancer. We also aimed to identify microRNAs that may regulate the expression of B7 family members. Methods: The Cancer Genome Atlas data from 1,092 patients with breast cancer, including gene expression, microRNA expression and survival data, were used for statistical and survival analyses. Polymerase chain reaction and Western blot were used to measure messenger RNA and protein expression, respectively. Luciferase assay was used to investigate direct microRNA target. Results: Bioinformatic analysis predicted that microRNA (miR)-93, miR-195, miR-497, and miR-340 are potential regulators of the immune evasion of breast cancer cells, and that they exert this function by targeting CD274, PDCD1LG2, and NCR3LG1. We chose CD274 for further investigations. We found that miR-195, miR-497, and CD274 expression levels were inversely correlated in MDA-MB-231 cells, and miR-195 and miR-497 expressions mimic inhibited CD274 expression in vitro. Mechanistic investigations demonstrated that miR-195 and miR-497 directly target CD274 3' untranslated region. Conclusion: Our data indicated that the level of B7 family members can predict the prognosis of breast cancer patients, and miR-195/miR-497 regulate CD274 expression in triple negative breast cancer. This regulation may further influence tumor progression and the immune tolerance mechanism in breast cancer and may be able to predict the effect of immunotherapy on patients.

• Asian Spine Journal
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• 제12권6호
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• pp.1010-1016
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• 2018

Study Design: Retrospective cohort study. Purpose: To report on spinal fusion assessment using computed tomography (CT) after adult spinal deformity (ASD) surgery using ultra-low dose recombinant human bone morphogenetic protein 2 (RhBMP-2). Overview of Literature: The reported dose of RhBMP-2 needed for successful spinal posterolateral fusion in ASD ranges from 10 to 20 mg per spinal level. This study reports the use of ultra-low dose of RhBMP-2 (0.07 mg per facet) to achieve spinal fusion in multilevel ASD surgery. Methods: Consecutive patients who underwent ASD surgery using ultra-low dose RhBMP-2 were recruited. Routine postoperative CT analysis for spinal fusion was performed by two spine surgeons. Inter-observer agreement was calculated for facet fusion (FF) and interbody fusion (IBF) at 6 and 12 months after the procedure. Results: Six consecutive ASD patients with a mean age of 62 years (28-72 years) were examined. Each patient received a total dose of 12 mg with an average dose of $0.69{\pm}0.2mg$ (0.42-1 mg) per single FF and $1.38{\pm}0.44mg$ (0.85-2 mg) for IBF. Total 131 FF and 15 IBF were examined in the study, with 88 FFs and nine IBFs being analyzed specifically at 6 months after the surgery. FF and IBF reported by surgeons A and B at 6 months were 97.7% vs. 91.9% FF, respectively (${\kappa}=0.95$) and 100% vs. 100% IBF, respectively (${\kappa}=1$). Two patients underwent longitudinal follow-up CT at 12 months, and the FF rates reported by surgeons A and B were 100% vs. 95.8%, respectively (${\kappa}=0.96$). Five out of nine facet (56%) non-unions were identified at the cross-links. The remaining four facet pseudarthrosis were noted at 1-2 spinal levels caudal to the cross-links. At the final clinical follow-up, there was no rod breakage, deformity progression, neurological deficit, or symptom recurrence. The Oswestry Disability Index improved by an average of $32.8{\pm}6.3$, while the mental component summary of the 36-item Short-Form Health Survey improved by an average of $4.7{\pm}2.1$, and physical component summary improved by an average of $10.5{\pm}2.1$. Conclusions: To our knowledge, this is the first study to report a CT that defined 92%-98% FF and 100% IBF using the lowest reported dose of RhBMP-2 in multilevel ASD surgery. The use of ultra-low dose RhBMP-2 reduces the RhBMP-2 related complications and healthcare costs.

• Nutrition Research and Practice
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• 제13권1호
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• pp.64-69
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• 2019

BACKGROUND/OBJECTIVES: Alzheimer's disease is a neurodegenerative disease that induces symptoms such as a decrease in motor function and cognitive impairment. Increases in the aggregation and deposition of amyloid beta protein ($A{\beta}$) in the brain may be closely correlated with the development of Alzheimer's disease. In this study, the effects of an adzuki bean extract on the aggregation of $A{\beta}$ were examined; moreover, the anti-Alzheimer's activity of the adzuki extract was examined. MATERIALS/METHODS: First, we undertook thioflavin T (ThT) fluorescence analysis and transmission electron microscopy (TEM) to evaluate the effect of an adzuki bean extract on $A{\beta}_{42}$ aggregation. To evaluate the effects of the adzuki extract on the symptoms of Alzheimer's disease in vivo, $A{\beta}_{42}$-overexpressing Drosophila were used. In these flies, overexpression of $A{\beta}_{42}$ induced the formation of $A{\beta}_{42}$ aggregates in the brain, decreased motor function, and resulted in cognitive impairment. RESULTS: Based on the results obtained by ThT fluorescence assays and TEM, the adzuki bean extract inhibited the formation of $A{\beta}_{42}$ aggregates in a concentration-dependent manner. When $A{\beta}_{42}$-overexpressing flies were fed regular medium containing adzuki extract, the $A{\beta}_{42}$ level in the brain was significantly lower than that in the group fed regular medium only. Furthermore, suppression of the decrease in motor function, suppression of cognitive impairment, and improvement in lifespan were observed in $A{\beta}_{42}$-overexpressing flies fed regular medium with adzuki extract. CONCLUSIONS: The results reveal the delaying effects of an adzuki bean extract on the progression of Alzheimer's disease and provide useful information for identifying novel prevention treatments for Alzheimer's disease.

• BMB Reports
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• 제52권5호
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• pp.318-323
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• 2019

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that present immunosuppressive effects in experimental and clinical trials targeting various rare diseases including inflammatory bowel disease (IBD). In addition, recent studies have reported tryptophanyl-tRNA synthetase (WRS) possesses uncanonical roles such as angiostatic and anti-inflammatory effects. However, little is known about the function of WRS in MSC-based therapy. In this study, we investigated if a novel factor, WRS, secreted from MSCs has a role in amelioration of IBD symptoms and determined a specific mechanism underlying MSC therapy. Experimental colitis was induced by administration of 3% DSS solution to 8-week-old mice and human umbilical cord blood-derived MSCs (hUCB-MSCs) were injected intraperitoneally. Secretion of WRS from hUCB-MSCs and direct effect of WRS on isolated $CD4^+$ T cells was determined via in vitro experiments and hUCB-MSCs showed significant therapeutic rescue against experimental colitis. Importantly, WRS level in serum of colitis induced mice decreased and recovered by administration of MSCs. Through in vitro examination, WRS expression of hUCB-MSCs increased when cells were treated with interferon-${\gamma}$ ($IFN-{\gamma}$). WRS was evaluated and revealed to have a role in inhibiting activated T cells by inducing apoptosis. In summary, $IFN-{\gamma}$-mediated secretion of WRS from MSCs has a role in suppressive effect on excessive inflammation and disease progression of IBD and brings new highlights in the immunomodulatory potency of hUCB-MSCs.

• Journal of Korean Neurosurgical Society
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• 제65권5호
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• pp.719-729
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• 2022

Objective : The ossification of the ligamentum flavum (OLF) is one of the major causes of thoracic myelopathy. Surgical decompression with or without instrumented fusion is the mainstay of treatment. However, few studies have reported on the added effect of instrumented fusion. The objective of this study was to compare clinical and radiological outcomes between surgical decompression without instrumented fusion (D-group) and that with instrumented fusion (F-group). Methods : A retrospective review was performed on 28 patients (D-group, n=17; F-group, n=11) with thoracic myelopathy due to OLF. The clinical parameters compared included scores of the Japanese Orthopedic Association (JOA), the Visual analogue scale of the back and leg (VAS-B and VAS-L), and the Korean version of the Oswestry disability index (K-ODI). Radiological parameters included the sagittal vertical axis (SVA), the pelvic tilt (PT), the sacral slope (SS), the thoracic kyphosis angle (TKA), the segmental kyphosis angle (SKA) at the operated level, and the lumbar lordosis angle (LLA; a negative value implying lordosis). These parameters were measured preoperatively, 1 year postoperatively, and 2 years postoperatively, and were compared with a linear mixed model. Results : After surgery, all clinical parameters were significantly improved in both groups, while VAS-L was more improved in the F-group than in the D-group (-3.4±2.5 vs. -1.3±2.2, p=0.008). Radiological outcomes were significantly different in terms of changes in TKA, SKA, and LLA. Changes in TKA, SKA, and LLA were 2.3°±4.7°, -0.1°±1.4°, and -1.3°±5.6° in the F-group, which were significantly lower than 6.8°±6.1°, 3.0°±2.8°, and 2.2°±5.3° in the D-group, respectively (p=0.013, p<0.0001, and p=0.037). Symptomatic recurrence of OLF occurred in one patient of the D-group at postoperative 24 months. Conclusion : Clinical improvement was achieved after decompression surgery for OLF regardless of whether instrumented fusion was added. However, adding instrumented fusion resulted in better outcomes in terms of lessening the progression of local and regional kyphosis and improving leg pain. Decompression with instrumented fusion may be a better surgical option for thoracic OLF.

• 디자인융복합연구
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• 제15권3호
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• pp.171-186
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• 2016

지속적인 노인인구의 증가와 고령화가 급속하게 진행되면서 지역 내 노인복지관은 지역주민의 다양한 욕구를 충족시키는 대표적인 서비스 공간으로 그 중요성이 높아지고 있다. 또한, 과거세대에 비해 높은 학력수준, 경제능력의 향상, 가치관과 라이프스타일이 변화됨에 따라 이전 세대와는 다르게 양질의 서비스를 추구하는 성향이 나타나고 있다. 이에 본 연구에서는 노인 연륜적 특성 지표인 라이프스타일 측정도구를 사용하여 노인의 라이프스타일 유형에 따른 노인복지관의 만족도를 분석하였다. 본 연구는 서울에 위치한 7곳의 노인복지관 이용자를 대상으로 설문조사를 실시하였다. 조사결과 첫째, 군집분석을 통해 라이프스타일 유형을 독립활동형, 보호활동형, 적극도전형, 소극도전형으로 분류하였다. 둘째, 노인의 라이프스타일에 따른 노인복지관의 전반적인 만족도는 보호활동형이 가장 높게 나타났으며 그 다음으로는 소극도전형, 적극도전형, 독립활동형의 순으로 나타났다. 셋째, 노인의 라이프스타일 유형별로 노인복지관의 공간특성이 만족도에 미치는 영향을 살펴본 결과 독립활동형과 소극도전형은 친밀성, 보호활동형은 쾌적성, 적극도전형은 편의성이 가장 영향력이 큰 것으로 조사되었다.

• Pediatric Infection and Vaccine
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• 제31권1호
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• pp.94-101
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• 2024

목적: 전세계적으로 코로나19에 대한 사회적 거리두기의 일환으로 보육시설에 대한 폐쇄, 휴원 및 재개원 등 영유아 대상 보육관련 정책에 변화가 있었다. 본 논문에서는 서울시에서 코로나19로 확진 영유아를 대상으로 인구학적, 역학적 특성을 파악하고, 연관이 있는 요인에 대한 분석을 하고자 하였다. 방법: 2020년 3월부터 2021년 12월까지 서울시에서 코로나19로 확진된 만 5세 미만의 영유아를 대상으로 역학조사서 및 집단발생 관련 자료를 분석하였다. 결과: 서울시 코로나19 확진 영유아는 총 5,025명이었다. 유증상자는 2,720명(54.1%)이며, 주된 증상은 발열(1,941명, 71.4%)이었다. 전체 코로나19 확진 영유아 중 96.4%는 기저질환이 없었다. 시간연장(야간, 24시, 휴일 등) 보육운영시설 비율이 높을수록 보육시설 관련 영유아 확진 비율이 높았음을 확인하였다. 결론: 영유아들의 낮은 중증화율과 치명률을 고려한 '일상 진료 시스템'과 같은 효율적인 모니터링 시스템이 필요할 것이다. 또한 무조건적인 폐쇄적 접근이 아닌, 과학적 근거에 기반하고 사회성 발달 과제를 놓치지 않을 수 있는 '감염병으로부터 안전한 보육 정책 마련'이라는 적절한 중재가 필요할 것이다.

• Korean Journal of Radiology
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• 제25권3호
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• pp.277-288
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• 2024

Objective: We previously found that the incidence of sarcopenia increased with declining glucose metabolism of muscle in patients with treatment-naïve diffuse large B-cell lymphoma (DLBCL). This study aimed to investigate the relationship between sarcopenia and muscle glucometabolism using ¹⁸F-FDG PET/CT at baseline and end-of-treatment, analyze the changes in these parameters through treatment, and assess their prognostic values. Materials and Methods: The records of 103 patients with DLBCL (median 54 years [range, 21-76]; male:female, 50:53) were retrospectively reviewed. Skeletal muscle area at the third lumbar vertebral (L3) level was measured, and skeletal muscle index (SMI) was calculated to determine sarcopenia, defined as SMI < 44.77 cm²/m² and < 32.50 cm²/m² for male and female, respectively. Glucometabolic parameters of the psoas major muscle, including maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean), were measured at L3 as well. Their changes across treatment were also calculated as ΔSMI, ΔSUVmax, and ΔSUVmean; Δbody mass index was also calculated. Associations between SMI and the metabolic parameters were analyzed, and their associations with progression-free survival (PFS) and overall survival (OS) were identified. Results: The incidence of sarcopenia was 29.1% and 36.9% before and after treatment, respectively. SMI (P = 0.004) was lower, and sarcopenia was more frequent (P = 0.011) at end-of-treatment than at baseline. The SUVmax and SUVmean of muscle were lower (P < 0.001) in sarcopenia than in non-sarcopenia at both baseline and end-of-treatment. ΔSMI was positively correlated with ΔSUVmax of muscle (P = 0.022). Multivariable Cox regression analysis showed that sarcopenia at end-of-treatment was independently negatively associated with PFS (adjusted hazard ratio [95% confidence interval], 2.469 [1.022-5.965]), while sarcopenia at baseline was independently negatively associated with OS (5.051 [1.453-17.562]). Conclusion: Sarcopenic patients had lower muscle glucometabolism, and the muscular and metabolic changes across treatment were positively correlated. Sarcopenia at baseline and end-of-treatment was negatively associated with the prognosis of DLBCL.