• 생명과학회지
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• 제34권4호
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• pp.227-235
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• 2024

약물이나 허브 제품으로 인한 간세포 손상은 이러한 화합물을 만성적으로 투여할 때 일어날 수 있는 중요한 문제 중 하나이다. 따라서 여러 가지의 치료 과정 중 간세포 생존율을 향상시키는 것은, 약물 적용에 있어 광범위한 기회를 제공할 수 있다. Valproic acid (VPA)는 자연적으로 발생하는 발레르산에서 파생된 분지형 단사슬 지방산으로 뇌전증과 발작을 치료하는 데 일반적으로 사용된다. 뿐만 아니라 VPA는 암, HIV 치료, 신경 퇴행성 질환에 수많은 효과를 발휘하지만, 간에 대한 VPA의 잠재적인 영향과 그 작용 메커니즘은 완전히 설명되지 않았다. 여기서, 우리는 VPA의 처리가 쥐 간세포(Hepa1c1c7)에서 PPAR 알파(PPAR-α)와 섬유아세포 성장 인자 21(FGF21)의 전사 수준을 증가시킨다는 것을 입증했다. VPA에 의해 유도된 FGF21 발현은 PPAR-α 결손 조건에서 상당히 억제되었다. 후속 실험에서 FGF21 신호 경로가 FGF 수용체 억제제에 의해 차단되었을 때, 간세포 생존력이 크게 억제되었음을 보여주었다. 마지막으로, 우리는 AMPK 인산화가 VPA에 의해 유도된 PPAR-α 증가에 작용하지 않는다는 것을 추가로 확인했다. 이러한 결과는 FGF21 발현의 증가가 VPA에 의해 유도된 간 독성을 완화시킬 수 있다는 것을 제시하며, 이와 같은 결과는 FGF21의 증감 여부가 VPA 치료 중 나타날 수 있는 간 손상을 예측하는 잠재적인 바이오마커로 사용될 수 있음을 제시한다.

• IMMUNE NETWORK
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• 제23권4호
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• pp.35.1-35.16
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• 2023

Defining the molecular dynamics associated with T cell differentiation enhances our understanding of T cell biology and opens up new possibilities for clinical implications. In this study, we investigated the dynamics of CD5 expression in CD8⁺ T cell differentiation and explored its potential clinical uses. Using PBMCs from 29 healthy donors, we observed a stepwise decrease in CD5 expression as CD8⁺ T cells progressed through the differentiation stages. Interestingly, we found that CD5 expression was initially upregulated in response to T cell receptor stimulation, but diminished as the cells underwent proliferation, potentially explaining the differentiation-associated CD5 downregulation. Based on the proliferation-dependent downregulation of CD5, we hypothesized that relative CD5 expression could serve as a marker to distinguish the heterogeneous CD8⁺ T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8⁺ T cells with higher CD5 expression exhibited phenotypic and functional characteristics resembling less differentiated cells compared to those with lower CD5 expression. Furthermore, in the retrospective analysis of PBMCs from 30 non-small cell lung cancer patients, we found that patients with higher CD5 expression in effector memory T cells displayed CD8⁺ T cells with a phenotype closer to the less differentiated cells, leading to favorable clinical outcomes in response to immune checkpoint inhibitor (ICI) therapy. These findings highlight the dynamics of CD5 expression as an indicator of CD8⁺ T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy.

• 대한영상의학회지
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• 제83권3호
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• pp.473-485
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• 2022

현대사회가 점차 고령화 사회가 됨에 따라 퇴행성 뇌질환의 발병률이 증가하고 있으며, 이러한 퇴행성 뇌질환에 관한 많은 연구들이 이루어지고 있다. 퇴행성 뇌질환의 진단에서 영상분석은 영상표지자로서 중요한 역할을 하고 있다. 영상분석에서 객관적이고 일관성 있는 평가는 퇴행성 뇌질환의 조기 진단 및 정확한 진단에 중요하다. 이에 다양한 퇴행성 뇌질환과 관련한 영상연구에 자기공명영상(이하 MRI)을 이용한 인공지능이 조기 진단과 최적의 치료 방향 계획 및 결정에 도움이 될 가능성을 보여주었다. 특히 MRI 기반의 뇌용적 측정과 분획화 및 특성을 포착하는 인공지능 소프트웨어들이 개발되고 연구되기 시작했다. 본 고찰에서는 우리나라에서 퇴행성 뇌질환과 관련하여 사용되고 있는 인공지능 소프트웨어의 현재 상황과 향후 인공지능 소프트웨어의 퇴행성 뇌질환 연구에의 활용, 그리고 인공지능 소프트웨어의 한계에 대해서 다루고자 한다.

• 대한영상의학회지
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• 제81권2호
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• pp.324-336
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• 2020

심혈관계 석회화는 다양한 심혈관계 질환에서 나타나며 심혈관 사건 발생의 표지자의 역할을 한다. CT의 기술이 발전함에 따라 심전도동기 CT뿐만이 아닌 비 심전도동기 CT에서도 심혈관계 석회화를 평가하는 것이 가능해졌다. 이번 종설에서는 비 조영증강 비 심전도동기 흉부 CT에서 발견되는 심혈관계 석회화를 심혈관 사건 발생과 연관되었다고 알려진 3가지 석회화(관상동맥, 흉부 대동맥, 판막 석회화)에 대해 자세히 살펴보고 추가적으로 우연적으로 발견될 수 있는 심막 석회화에 대해서도 간단히 기술하였다. 우리나라에서 2019년 하반기부터 폐암 검진이 시작되면서 고령 흡연자의 비 조영증강 비 심전도동기 저선량 CT의 영상의 수가 늘어나고 있고 이에 우연히 발견되는 심혈관계 석회화도 늘어나고 있다. 그러므로 비 조영증강 비 심전도동기 흉부 CT에서 발견되는 심혈관계 석회화의 의미를 이해하고 적절히 보고하는 것이 영상의학과 의사에게 중요할 것이다.

• Korean Journal of Radiology
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• 제23권1호
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• pp.77-88
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• 2022

Objective: Our study aimed to evaluate the quality of radiomics studies on brain metastases based on the radiomics quality score (RQS), Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) checklist, and the Image Biomarker Standardization Initiative (IBSI) guidelines. Materials and Methods: PubMed MEDLINE, and EMBASE were searched for articles on radiomics for evaluating brain metastases, published until February 2021. Of the 572 articles, 29 relevant original research articles were included and evaluated according to the RQS, TRIPOD checklist, and IBSI guidelines. Results: External validation was performed in only three studies (10.3%). The median RQS was 3.0 (range, -6 to 12), with a low basic adherence rate of 50.0%. The adherence rate was low in comparison to the "gold standard" (10.3%), stating the potential clinical utility (10.3%), performing the cut-off analysis (3.4%), reporting calibration statistics (6.9%), and providing open science and data (3.4%). None of the studies involved test-retest or phantom studies, prospective studies, or cost-effectiveness analyses. The overall rate of adherence to the TRIPOD checklist was 60.3% and low for reporting title (3.4%), blind assessment of outcome (0%), description of the handling of missing data (0%), and presentation of the full prediction model (0%). The majority of studies lacked pre-processing steps, with bias-field correction, isovoxel resampling, skull stripping, and gray-level discretization performed in only six (20.7%), nine (31.0%), four (3.8%), and four (13.8%) studies, respectively. Conclusion: The overall scientific and reporting quality of radiomics studies on brain metastases published during the study period was insufficient. Radiomics studies should adhere to the RQS, TRIPOD, and IBSI guidelines to facilitate the translation of radiomics into the clinical field.

• IMMUNE NETWORK
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• 제21권6호
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• pp.43.1-43.14
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• 2021

Group 3 innate lymphoid cells (ILC3), which express IL-22 and IL-17A, has been introduced as one of pathologic cells in axial spondyloarthritis (axSpA). Dyslipidaemia should be managed in axSpA patients to reduce cardiovascular disease, and dyslipidaemia promotes inflammation. This study aimed to reveal the role of circulating ILC3 in axSpA and the impact of dyslipidaemia on axSpA pathogenesis. AxSpA patients with or without dyslipidaemia and healthy control were recruited. Peripheral blood samples were collected, and flow cytometry analysis of circulating ILC3 and CD4⁺ T cells was performed. The correlation between Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP) and circulating immune cells was evaluated. The effect of oxidized low-density lipoprotein cholesterol (oxLDL-C) on immune cell differentiation was confirmed. AxSpA human monocytes were cultured with with oxLDL-C, IL-22, or oxLDL-C plus IL-22 to evaluate osteoclastogenesis using tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative PCR of osteoclast-related gene expression. Total of 34 axSpA patients (13 with dyslipidaemia and 21 without) were included in the analysis. Circulating IL-22⁺ ILC3 and Th17 were significantly elevated in axSpA patients with dyslipidaemia (p=0.001 and p=0.034, respectively), and circulating IL-22⁺ ILC3 significantly correlated with ASDAS-CRP (Rho=0.4198 and p=0.0367). Stimulation with oxLDL-C significantly increased IL-22⁺ ILC3, NKp44^- ILC3, and Th17 cells, and these were reversed by CD36 blocking agent. IL-22 and oxLDL-C increased TRAP⁺ cells and osteoclast-related gene expression. This study suggested potential role of circulating IL-22⁺ ILC3 as biomarker in axSpA. Furthermore, dyslipidaemia augmented IL-22⁺ ILC3 differentiation, and oxLDL-C and IL-22 markedly increased osteoclastogenesis of axSpA.

• Animal Bioscience
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• 제37권7호
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• pp.1213-1224
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• 2024

Objective: Enterotypes (ETs) are the clustering of gut microbial community structures, which could serve as indicators of growth performance and carcass traits. However, ETs have been sparsely investigated in waterfowl. The objective of this study was to identify the ileal ETs and explore the correlation of the ETs with growth performance and carcass traits in Muscovy ducks. Methods: A total of 200 Muscovy ducks were randomly selected from a population of 5,000 ducks at 70-day old, weighed and slaughtered. The growth performance and carcass traits, including body weight, dressed weight and evidenced weight, dressed percentage, percentage of apparent yield, breast muscle weight, leg muscle weight, percentage of leg muscle and percentage of breast muscle, were determined. The contents of ileum were collected for the isolation of DNA and 16S rRNA gene sequencing. The ETs were identified based on the 16S rRNA gene sequencing data and the correlation of the ETs with growth performance and carcass traits was performed by Spearman correlation analysis. Results: Three ETs (ET1, ET2, and ET3) were observed in the ileal microbiota of Muscovy ducks with significant differences in number of features and α-diversity among these ETs (p<0.05). Streptococcus, Candida Arthritis, and Bacteroidetes were the presentative genus in ET1 to ET3, respectively. Correlation analysis revealed that Lactococcus and Bradyrhizobium were significantly correlated with percentage of eviscerated yield and leg muscle weight (p<0.05) while ETs were found to have a close association with percentage of eviscerated yield, leg muscle weight, and percentage of leg muscle in Muscovy ducks. However, the growth performance of ducks with different ETs did not show significant difference (p>0.05). Lactococcus were found to be significantly correlated with leg muscle weight, dressed weight, and percentage of eviscerated yield. Conclusion: Our findings revealed a substantial variation in carcass traits associated with ETs in Muscovy ducks. It is implied that ETs might have the potential to serve as a valuable biomarker for assessing duck carcass traits. It would provide novel insights into the interaction of gut microbiota with growth performance and carcass traits of ducks.

• Journal of Ecology and Environment
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• 제48권1호
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• pp.24-31
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• 2024

Background: Honey from different geographical origins can have distinct characteristics due to variations in the floral sources available to stingless bees in different regions. The most abundant stingless bee for meliponiculture in Thailand is Tetragonula pagdeni. However, only a few studies about the properties of honey from a different origin were carried out. The objective of this study was focused on a comparative study to evaluate the melissopalynological, physicochemical, antioxidant activities, and total phenolic contents (TPCs) of stingless bee honey produced by T. pagdeni from different parts of Thailand. Results: Fifty honey samples were collected from five locations, and the physicochemical properties of T. pagdeni honey samples are acidic (pH 3.02-4.15) and have a high water content (18.42-25.06 %w/w), which is related to the regions of meliponary. Melisopalynological analysis reveals the predominant pollen from Melaleuca quinquenervia, Cocus nuciferca, Nephelium lappaceum, Salacca wallichiana, and multiflora honey. All honey samples were analyzed for their TPC and 2,2-diphenyl1-picrylhydrazyl radical scavenging activity. The results show that all samples had high TPC and antioxidant activities with a strong correlation (p < 0.05). Conclusions: The data from this study indicates the importance of geographical origin, which links physicochemical properties, phenolic compounds, and functional characteristics to their floral. Besides, the floral sources and harvesting location affected the properties of stingless bee honey. Our results identify Melaleuca honey as a promising source of phenolic content and antioxidant activity that can be used as a functional food, as well as multiflora and Cocus honey. However, further studies are required to characterize the phenolic compound and its biological potential, which could be a stingless bee honey biomarker and quality control, simultaneously with the physicochemical analysis.

• Journal of Animal Science and Technology
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• 제66권5호
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• pp.1021-1033
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• 2024

Exosomes have been extensively studied as disease biomarker in humans, given their role in transporting bioactive molecules. However, despite the great potential of exosomes as noninvasive diagnostic markers and therapeutic nanocarriers for bovine diseases, few studies have been conducted on bovine exosome. Thus, this study aimed to quantitatively and qualitatively compare three isolation methods to identify a suitable method for bovine serum. Exosomes were isolated using ultracentrifugation alone (UC), a combination of ultracentrifugation and size exclusion chromatography (US), or membrane affinity-based exoEasy kit (EE). Isolated particles were evaluated using a range of complementary techniques. Transmission electron microscopy showed that all three isolation methods resulted in particles with a cup-shaped morphology. The particle concentration measured by nanoparticle trafficking analyzer of US was lower compared to those of UC and EE method. As a result of immunoblotting, exosome markers including TSG101, CD81, and HSP70 were detected in US particles, while in UC and EE, only TSG101 expression was confirmed. Particles isolated from UC and EE showed a contamination with the blood protein albumin, whereas particles from US did not show albumin contamination. In addition, to evaluate the possibility of using exosomes as biomarkers, the profiles of the small RNA in the exosomes were compared using the bioanalyzer 2100. As a result, in the EE method, the band of small RNA (25-200 nt) was most prominent, and in the US methods, a distinct band was observed in the small RNA range. Collectively, the purity of exosomes without non-exosomal contamination was highest in the US method. However, for the detection of small RNA, the EE method was found to be the most suitable. Therefore, the results suggest that the optimal isolation method varies depending on the specific purpose of exosome isolation.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제27권5호
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• pp.322-331
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• 2024

Purpose: Human breast milk (HBM) contains immune components that produced and delivered from the mother along with nutrients necessary for the baby. MicroRNA (miRNA) is a small noncoding RNA molecule, that is used as an ideal biomarker for diagnosis and prognosis of various diseases and are more abundant in HBM. We analyzed and compared the immune components and miRNAs of HBM. Methods: HBM were collected from 20 healthy breastfeeding mothers. We measured the amount of lactoferrin, lysozyme, and immunoglobulin A (IgA) and extracted the miRNAs from each breast milk samples. Next, the top 5 and bottom 5 expressed miRNAs were compared and analyzed based on the amounts of the 3 immune components. Results: The mean levels and ranges of lactoferrin, lysozyme, and IgA were 6.33 (2.24-14.77)×10⁶ ng/mL, 9.90 (1.42-17.59)×10⁷ pg/mL, and 6.64 (0.48-20.01)×10⁵ ng/mL, respectively. The miRNAs concentration per 1 mL of skim milk was 40.54 (14.95-110.01) ng/μL. Comparing the bottom 5 and top 5 groups of each immune component, 19 miRNAs were significantly upregulated (6, 9, and 4 targeting lactoferrin, lysozyme, and IgA, respectively) and 21 were significantly downregulated (4, 9, and 8 targeting lactoferrin, lysozyme, and IgA, respectively). There were no miRNAs that were expressed significantly higher or lower in common to all 3 components. However, 2 and 3 miRNAs were commonly overexpressed and underexpressed, in the top 5 groups of lysozyme and IgA concentrations. Conclusion: We identified the immune components and miRNAs in breast milk and found that each individual has different ingredients.