• IMMUNE NETWORK
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• 제20권5호
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• pp.40.1-40.15
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• 2020

The protein encoded by the Gene Associated with Retinoid-Interferon-Induced Mortality-19 (GRIM-19) is located in the mitochondrial inner membrane and is homologous to the NADH dehydrogenase 1-alpha subcomplex subunit 13 of the electron transport chain. Multiple sclerosis (MS) is a demyelinating disease that damages the brain and spinal cord. Although both the cause and mechanism of MS progression remain unclear, it is accepted that an immune disorder is involved. We explored whether GRIM-19 ameliorated MS by increasing the levels of inflammatory cytokines and immune cells; we used a mouse model of experimental autoimmune encephalomyelitis (EAE) to this end. Six-to-eight-week-old male C57BL/6, IFNγ-knockout (KO), and GRIM-19 transgenic mice were used; EAE was induced in all strains. A GRIM-19 overexpression vector (GRIM19 OVN) was electrophoretically injected intravenously. The levels of Th1 and Th17 cells were measured via flow cytometry, immunofluorescence, and immunohistochemical analysis. IL-17A and IFNγ expression levels were assessed via ELISA and quantitative PCR. IL-17A expression decreased and IFNγ expression increased in EAE mice that received injections of the GRIM-19 OVN. GRIM19 transgenic mice expressed more IFNγ than did wild-type mice; this inhibited EAE development. However, the effect of GRIM-19 overexpression on the EAE of IFNγ-KO mice did not differ from that of the empty vector. GRIM-19 expression was therapeutic for EAE mice, elevating the IFNγ level. GRIM-19 regulated the Th17/Treg cell balance.

• Molecules and Cells
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• 제47권3호
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• pp.100033.1-100033.13
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• 2024

Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.

• Korean Journal of Radiology
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• 제21권9호
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• pp.1077-1086
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• 2020

Objective: To evaluate the effect of perfluorobutane microbubbles (Sonazoid^®, GE Healthcare) on steam popping during radiofrequency (RF) ablation for treating hepatocellular carcinoma (HCC), and to assess whether popping affects treatment outcomes. Materials and Methods: The institutional review board approved this retrospective study, which included 90 consecutive patients with single HCC, who received percutaneous RF ablation as the first-line treatment. The patients were divided into two groups, based on the presence or absence of the popping phenomenon, which was defined as an audible sound with a simultaneous sudden explosion within the ablation zone as detected via ultrasonography during the procedure. The factors contributing to the popping phenomenon were identified using multivariable logistic regression analysis. Local tumor progression (LTP) and disease-free survival (DFS) were assessed using the Kaplan-Meier method with the log-rank test for performing comparisons between the two groups. Results: The overall incidence of the popping phenomenon was 25.8% (24/93). Sonazoid^® was used in 1 patient (4.2%) in the popping group (n = 24), while it was used in 15 patients (21.7%) in the non-popping group (n = 69). Multivariable analysis revealed that the use of Sonazoid^® was the only significant factor for absence of the popping phenomenon (odds ratio = 0.10, p = 0.048). There were no significant differences in cumulative LTP and DFS between the two groups (p = 0.479 and p = 0.424, respectively). Conclusion: The use of Sonazoid^® has a suppressive effect on the popping phenomenon during RF ablation in patients with HCC. However, the presence of the popping phenomenon may not affect clinical outcomes.

• Korean Journal of Radiology
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• 제21권6호
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• pp.707-716
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• 2020

Objective: To evaluate pharmacokinetic variables from contrast-enhancing lesions (CELs) and non-enhancing T2 high signal intensity lesions (NE-T2HSILs) on dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging for predicting progression-free survival (PFS) in glioblastoma (GBM) patients. Materials and Methods: Sixty-four GBM patients who had undergone preoperative DCE MR imaging and received standard treatment were retrospectively included. We analyzed the pharmacokinetic variables of the volume transfer constant (Ktrans) and volume fraction of extravascular extracellular space within the CEL and NE-T2HSIL of the entire tumor. Univariate and multivariate Cox regression analyses were performed using preoperative clinical characteristics, pharmacokinetic variables of DCE MR imaging, and postoperative molecular biomarkers to predict PFS. Results: The increased mean Ktrans of the CEL, increased 95th percentile Ktrans of the CELs, and absence of methylated O⁶-methylguanine-DNA methyltransferase promoter were relevant adverse variables for PFS in the univariate analysis (p = 0.041, p = 0.032, and p = 0.083, respectively). The Kaplan-Meier survival curves demonstrated that PFS was significantly shorter in patients with a mean Ktrans of the CEL > 0.068 and 95th percentile Ktrans of the CEL > 0.223 (log-rank p = 0.038 and p = 0.041, respectively). However, only mean Ktrans of the CEL was significantly associated with PFS (p = 0.024; hazard ratio, 553.08; 95% confidence interval, 2.27-134756.74) in the multivariate Cox proportional hazard analysis. None of the pharmacokinetic variables from NE-T2HSILs were significantly related to PFS. Conclusion: Among the pharmacokinetic variables extracted from CELs and NE-T2HSILs on preoperative DCE MR imaging, the mean Ktrans of CELs exhibits potential as a useful imaging predictor of PFS in GBM patients.

• 대한한방내과학회지
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• 제45권2호
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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.

• Korean Journal of Radiology
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• 제21권12호
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• pp.1317-1325
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• 2020

Objective: The aim of this study was to prospectively evaluate whether liver stiffness (LS) assessments, obtained by two-dimensional (2D)-shear wave elastography (SWE) with a propagation map, can evaluate liver fibrosis stage using histopathology as the reference standard. Materials and Methods: We prospectively enrolled 123 patients who had undergone percutaneous liver biopsy from two tertiary referral hospitals. All patients underwent 2D-SWE examination prior to biopsy, and LS values (kilopascal [kPa]) were obtained. On histopathologic examination, fibrosis stage (F0-F4) and necroinflammatory activity grade (A0-A4) were assessed. Multivariate linear regression analysis was performed to determine the significant factors affecting the LS value. The diagnostic performance of the LS value for staging fibrosis was assessed using receiver operating characteristic (ROC) analysis, and the optimal cut-off value was determined by the Youden index. Results: Reliable measurements of LS values were obtained in 114 patients (92.7%, 114/123). LS values obtained from 2D-SWE with the propagation map positively correlated with the progression of liver fibrosis reported from histopathology (p < 0.001). According to the multivariate linear regression analysis, fibrosis stage was the only factor significantly associated with LS (p < 0.001). The area under the ROC curve of LS from 2D-SWE with the propagation map was 0.773, 0.865, 0.946, and 0.950 for detecting F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The optimal cut-off LS values were 5.4, 7.8, 9.4, and 12.2 kPa for F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The corresponding sensitivity and specificity of the LS value for detecting cirrhosis were 90.9% and 88.4%, respectively. Conclusion: The LS value obtained from 2D-SWE with a propagation map provides excellent diagnostic performance in evaluating liver fibrosis stage, determined by histopathology.

• 한국학교ㆍ지역보건교육학회지
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• 제25권1호
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• pp.1-15
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• 2024

목적: 본 연구는 청·중년 고혈압환자의 일반적 특성과 신체활동 특성을 살펴보고, 주요 영향 요인을 파악하여 보건의료 정책제언을 제공하는 데 목적이 있다. 방법: 연구의 대상자는 2021년 지역사회건강조사에서 청년과 중년(19세~49세)의 고혈압 진단자 5,511명이다. 수집된 자료의 SPSS 26.0으로 분석하였다. 결과: 모형 1은 일반적인 특성에 따른 청·중년 고혈압환자의 영향 요인으로 설명력은 R²= .065이다. 경제활동 유무(𝛽= -.219, p<.001), 주당 아침 식사 횟수(𝛽= .117, p<.001), 성별(𝛽= .090, p<.001), 주관적 건강상태(𝛽= .073, p<.001), 교육 수준(𝛽= .069, p<.001) 순이다. 모형 2는 신체활동 특성을 포함한 청·중년 고혈압 환자의 영향 요인으로 설명력 R²= .076이다. 근력운동 일수(𝛽= -4.791, p<.001), 걷기 실천 일수(𝛽= -2.694, p<.01), 고강도 신체활동(𝛽= -2.629, p<.01) 순이다. 결론: 청·중년 고혈압의 적극적인 관리는 심각한 질환으로의 진행을 예방하는 데 필수적이다. 청·중년의 고혈압 예방을 위해서는 일반적 특성과 신체활동 특성을 고려한 건강증진 프로그램을 개발하고 활용하는 보건교육이 필요하다.

• BMB Reports
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• 제57권3호
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• pp.161-166
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• 2024

Aberrant DNA methylation plays a critical role in the development and progression of colorectal cancer (CRC), which has high incidence and mortality rates in Korea. Various CRC-associated methylation markers for cancer diagnosis and prognosis have been developed; however, they have not been validated for Korean patients owing to the lack of comprehensive clinical and methylome data. Here, we obtained reliable methylation profiles for 228 tumor, 103 adjacent normal, and two unmatched normal colon tissues from Korean patients with CRC using an Illumina Infinium EPIC array; the data were corrected for biological and experiment biases. A comparative methylome analysis confirmed the previous findings that hypermethylated positions in the tumor were highly enriched in CpG island and promoter, 5' untranslated, and first exon regions. However, hypomethylated positions were enriched in the open-sea regions considerably distant from CpG islands. After applying a CpG island methylator phenotype (CIMP) to the methylome data of tumor samples to stratify the CRC patients, we consolidated the previously established clinicopathological findings that the tumors with high CIMP signatures were significantly enriched in the right colon. The results showed a higher prevalence of microsatellite instability status and MLH1 methylation in tumors with high CMP signatures than in those with low or non-CIMP signatures. Therefore, our methylome analysis and dataset provide insights into applying CRC-associated methylation markers for Korean patients regarding cancer diagnosis and prognosis.

• 대한영상의학회지
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• 제84권3호
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• pp.736-744
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• 2023

성인형 알렉산더병은 운동 실조, 경련성 마비 또는 뇌간 징후를 나타내는 드문 유전 질환이다. 성인형 알렉산더병의 진단은 흔히 자기공명영상 검사 소견을 통해 내려진다. 이에 저자들은 glial fibrillary acidic protein (이하 GFAP) 유전자 변이 분석을 통해 확진된 37세와 61세 성인형 알렉산더병 환자의 특징적인 자기공명영상 소견과 추적 검사상 변화 사례에 대해 보고하고자 한다. 자기공명영상에서 환자들은 전형적인 뇌간 위축과 백질 이상 소견을 보였다. 특징적인 자기공명영상을 바탕으로 추정진단을 내렸으며 이후 GFAP 유전자 변이 분석을 통해 확진되었다. 또한, 추적 관찰 검사에서 연수와 상부 경부 척수 위축의 진행을 보였다. 이러한 성인형 알렉산더병의 특징적인 자기공명영상 소견에 대한 이해를 바탕으로, 감별진단을 위한 GFAP 유전자 검사 시행 결정에 도움이 될 수 있을 것이다.

• 한방비만학회지
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• 제24권1호
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• pp.25-40
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• 2024

Objectives: In the present study, we investigated the effects of clean-diabetes mellitus 3 (C-DM3), a herbal formula with Trichosanthis Radix, Coptidis Rhizoma, Crataegi Fructus, and Cinnamomi Cortex, on the pathological and serological symptoms of diabetes and its related molecular mechanisms in diet-induced obese mice. Methods: We prepared an obese mouse model using a high-fat diet for 8 weeks and then administered the C-DM3 extract for 4 weeks. The changes of pathological and serological biomarkers for diabetes assessment were measured in the mice and histological changes were observed in the liver and pancreas tissues. We also identified the main compounds in the C-DM3 extract using high pressure liquid chromatography (HPLC) and analyzed the molecular mechanism of the disease condition by network pharmacological analysis. Results: In the in vivo, the administration of C-DM extract to obese mice significantly reduced body weight gain, fatty liver symptoms, and muscle loss, and decreased the levels of fasting blood glucose, insulin, aspertate aminotransferase, triglycerides, and low-density lipoprotein-cholesterol. In addition, C-DM extract significantly increased the phosphorylation of insulin receptor substrate 1, protein kinase b (AKT), phosphoinositide 3-kinase (PI3K), adenosine monophosphate-activated protein kinase, and glucose transporter 4 in all pancreatic and liver tissues, with inhibition of histopathological changes in obese mice. HPLC analysis identified hyperoside, berberine, epiberberine, columbamin, coptisine, coumarin, jatrorrhizine, and citric acid as the main compounds. In the network pharmacological analysis, the molecular targets of C-DM3 extract on obesity and diabetes were shown as the insulin, AKT, PI3K, and mitogen-activated protein kinase pathways with the regulation of inflammatory molecules interleukin 6 (IL-6), jun proto-oncogene, and IL-1β, which matched our in vivo targets. Conclusions: Based on these results, C-DM3 extract is expected to be effective in improving obesity and preventing diabetic progression.