• Korean Journal of Radiology
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• 제22권12호
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• pp.2052-2061
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• 2021

Objective: The role of preoperative overt hepatic encephalopathy (OHE) in the neurophysiological mechanism of cognitive improvement after liver transplantation (LT) remains elusive. This study aimed to explore changes in sub-regional thalamic functional connectivity (FC) after LT and their relationship with neuropsychological improvement using resting-state functional MRI (rs-fMRI) data in cirrhotic patients with and without a history of OHE. Materials and Methods: A total of 51 cirrhotic patients, divided into the OHE group (n = 21) and no-OHE group (n = 30), and 30 healthy controls were enrolled in this prospective study. Each patient underwent rs-fMRI before and 1 month after LT. Using 16 bilateral thalamic subregions as seeds, we conducted a seed-to-voxel FC analysis to compare the thalamic FC alterations before and after LT between the OHE and no-OHE groups, as well as differences in FC between the two groups of cirrhotic patients and the control group. Correction for multiple comparisons was conducted using the false discovery rate (p < 0.05). Results: We found abnormally increased FC between the thalamic sub-region and prefrontal cortex, as well as an abnormally decreased FC between the bilateral thalamus in both OHE and no-OHE cirrhotic patients before LT, which returned to normal levels after LT. Compared with the no-OHE group, the OHE group exhibited more extensive abnormalities prior to LT, and the increased FC between the right thalamic subregions and right inferior parietal lobe was markedly reduced to normal levels after LT. Conclusion: The renormalization of FC in the cortico-thalamic loop might be a neuro-substrate for the recovery of cognitive function after LT in cirrhotic patients. In addition, hyperconnectivity between thalamic subregions and the inferior parietal lobe might be an important feature of OHE. Changes in FC in the thalamus might be used as potential biomarkers for recovery of cognitive function after LT in cirrhotic patients.

• Animal Bioscience
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• 제37권8호
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• pp.1317-1332
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• 2024

Objective: Rare study of the non-coding and regulatory regions of the genome limits our ability to decode the mechanisms of fatty liver hemorrhage syndrome (FLHS) in chickens. Methods: Herein, we constructed the high-fat diet-induced FLHS chicken model to investigate the genome-wide active enhancers and transcriptome by H3K27ac target chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-Seq) profiles of normal and FLHS liver tissues. Concurrently, an integrative analysis combining ChIP-seq with RNA-Seq and a comparative analysis with chicken FLHS, rat non-alcoholic fatty liver disease (NAFLD) and human NAFLD at the transcriptome level revealed the enhancer and super enhancer target genes and conservative genes involved in metabolic processes. Results: In total, 56 and 199 peak-genes were identified in upregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange) ≥1) (PP) and downregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange)≤-1) (PN), respectively; then we screened key regulatory targets mainly distributing in lipid metabolism (PCK1, APOA4, APOA1, INHBE) and apoptosis (KIT, NTRK2) together with MAPK and PPAR signaling pathway in FLHS. Intriguingly, PCK1 was also significantly covered in up-regulated super-enhancers (SEs), which further implied the vital role of PCK1 during the development of FLHS. Conclusion: Together, our studies have identified potential therapeutic biomarkers of PCK1 and elucidated novel insights into the pathogenesis of FLHS, especially for the epigenetic perspective.

• Journal of Microbiology and Biotechnology
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• 제33권12호
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• pp.1648-1656
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• 2023

We have previously observed that feeding with single-cell hemoprotein (heme-SCP) in dogs (1 g/day for 6 days) and broiler chickens (1 ppm for 32 days) increased the proportion of lactic acid bacteria in the gut while reducing their body weights by approximately 1~2%. To define the roles of heme-SCP in modulating body weight and gut microbiota, obese C57BL/6N mice were administered varied heme-SCP concentrations (0, 0.05, and 0.5% heme-SCP in high fat diet) for 28 days. The heme-SCP diet seemed to restrain weight gain till day 14, but the mice gained weight again later, showing no significant differences in weight. However, the heme-SCP-fed mice had stiffer and oilier bodies compared with those of the control mice, which had flabby bodies and dull coats. When mice were dissected at day 10, the obese mice fed with heme-SCP exhibited a reduction in subcutaneous fat with an increase in muscle mass. The effect of heme-SCP on the obesity-associated dyslipidemia tended to be corroborated by the blood parameters (triglyceride, total cholesterol, and C-reactive protein) at day 10, though the correlation was not clear at day 28. Notably, the heme-SCP diet altered gut microbiota, leading to the proliferation of known anti-obesity biomarkers such as Akkermansia, Alistipes, Oscillibacter, Ruminococcus, Roseburia, and Faecalibacterium. This study suggests the potential of heme-SCP as an anti-obesity supplement, which modulates serum biochemistry and gut microbiota in high-fat diet-induced obese mice.

• 대한한의학방제학회지
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• 제32권1호
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• pp.11-28
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• 2024

Objectives : GunRyeong-Tang(GRT) is a traditional herbal prescription that combines Oryeongsan and Sagunja-tang. This study employed network analysis methods on the components of GRT and target genes related to diabetes complications to predict the improvement effects of GRT on diabetes complications. Methods : The collection of active compounds of GRT and related target genes involved the utilization of public databases and the PubChem database. We selected diabetes complication-related genes using GeneCards and confirmed their correlation through comparative analysis with the target genes of GRT. We constructed a network using Cytoscape 3.9.1 and conducted topological analysis. To predict the mechanism, we performed functional enrichment analysis based on Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Results : Through network analysis, 234 active compounds and 1361 related genes were collected from GRT. A total of 9,136 genes related to diabetes complications were collected, and 1,039 target genes overlapping with the components of GRT were identified. The core genes of this network were TP53, INS, AKT1, ALB, and EGFR. In addition, GRT significantly reduced the H9c2 cell size and the expression of myocardial hypertrophy biomarkers (ANP, BNP), which were increased by high glucose (HG). Conclusions : Through this study, we were able to predict the activity and mechanism of action of GRT on diabetes and diabetic complications, and confirmed the potential of GRT as a treatment for diabetes complications through the effect of GRT on improving myocardial hypertrophy for diabetic cardiomyopathy.

• 한국발생생물학회지:발생과생식
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• 제27권4호
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• pp.185-193
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• 2023

Although increasing evidence of cause-and-effect relationship between BPA exposure and female reproductive disorders have been suggested through many studies, the precise biochemical and molecular mechanism(s) by which BPA interferes with steroidogenesis in the ovarian cells still remain unclear. Therefore, the purpose of this study was to discover the steroidogenic biomarker(s) associated with BPA treatment in human granulosa cell line, KGN. In this study, our results obtained via the analysis of steroidogenesis-related protein expression in KGN cells using quantitative polymerase chain reaction (qPCR) and western blot analyses revealed that the expression levels of steroidogenic acute regulatory (StAR) and aromatase decreased considerably and gradually after BPA treatment in a dose-dependent manner under BPA treatment. Further, remarkable decreases in their expression levels at the cellular levels were also confirmed via immunocytochemistry, and subsequent StAR and aromatase mRNA expression levels showed profiles similar to those observed for their proteins, i.e., both StAR and aromatase mRNA expression levels were significantly decreased under BPA treatment at concentrations ≥0.1 μM. We observed that follicle stimulating hormone upregulated StAR and aromatase protein expression levels; however, this effect was suppressed in the presence of BPA. Regarding the steroidogenic effects of BPA on KGN cells, controversies remain regarding the ultimate outcomes. Nevertheless, we believe that the results here presented imply that KGN cells have a good cellular and steroidogenic machinery for evaluating endocrine disruption. Therefore, StAR and aromatase could be stable and sensitive biomarkers in KGN cells for the cellular screening of the potential risk posed by exogenous and environmental chemicals to female reproductive (endocrine) function.

• Clinical and Experimental Reproductive Medicine
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• 제50권4호
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• pp.253-261
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• 2023

Objective: Azoospermia (the total absence of sperm in the ejaculate) affects approximately 10% of infertile males. Despite diagnostic advances, azoospermia remains the most challenging issue associated with infertility treatment. Our study evaluated transition nuclear protein 2 (TNP2) and synaptonemal complex protein 3 (SYCP3) polymorphisms, azoospermia factor a (AZFa) microdeletion, and gene expression levels in 100 patients with azoospermia. Methods: We investigated a TNP2 single-nucleotide polymorphism through polymerase chain reaction (PCR) restriction fragment length polymorphism analysis using a particular endonuclease. An allele-specific PCR assay for SYCP3 was performed utilizing two forward primers and a common reverse primer in two PCR reactions. Based on the European Academy of Andrology guidelines, AZFa microdeletions were evaluated by multiplex PCR. TNP2, SYCP3, and the AZFa region main gene (DEAD-box helicase 3 and Y-linked [DDX3Y]) expression levels were assessed via quantitative PCR, and receiver operating characteristic curve analysis was used to determine the diagnostic capability of these genes. Results: The TNP2 genotyping and allelic frequency in infertile males did not differ significantly from fertile volunteers. In participants with azoospermia, the allelic frequency of the SYCP3 mutant allele (C allele) was significantly altered. Deletion of sY84 and sY86 was discovered in patients with azoospermia and oligozoospermia. Moreover, SYCP3 and DDX3Y showed decreased expression levels in the azoospermia group, and they exhibited potential as biomarkers for diagnosing azoospermia (area under the curve, 0.722 and 0.720, respectively). Conclusion: These results suggest that reduced SYCP3 and DDX3Y mRNA expression profiles in testicular tissue are associated with a higher likelihood of retrieving spermatozoa in individuals with azoospermia. The homozygous genotype TT of the SYCP3 polymorphism was significantly associated with azoospermia.

• 대한치매학회지
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• 제23권2호
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• pp.95-106
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• 2024

Background and Purpose: Ventricle enlargement has been implicated in the pathophysiology of Alzheimer's disease (AD). We studied the relationship between ventricular size and cognitive function in patients with AD. We focused on the effect of the initial ventricle size on the rate of cognitive decline in patients with AD. Methods: A retrospective analysis of probable clinical AD participants with more than 2 magnetic resonance imaging images was performed. To measure ventricle size, we used visual rating scales of (1) Cardiovascular Health Study (CHS) score and (2) conventional linear measurement method. Results: Increased clinical dementia rating (CDR) was correlated with a decreased Mini-Mental Status Examination (MMSE) score, and increased medial temporal lobe atrophy (MTLA) and global ventricle size (p<0.001, p<0.001, p=0.021, respectively). There was a significant correlation between the change in cognitive function in the group (70%-100%ile) with a large initial ventricle size (p=0.021 for ∆CDR, p=0.01 for ∆MMSE), while the median ventricle size (30%-70%ile) showed correlation with other brain structural changes (MTLA, frontal atrophy [FA], and white matter) (p=0.036 for initial MTLA, p=0.034 for FA). Conclusions: In this study, the initial ventricle size may be a potential new imaging biomarker for initial cognitive function and clinical progression in AD. We found a relationship between the initial ventricle size and initial AD-related brain structural biomarkers.

• 방사선산업학회지
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• 제17권4호
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• pp.417-425
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• 2023

Lutetium(¹⁷⁷Lu), with its theranostic properties, is one of the most widely used radioisotopes and has a large share of the radiopharmaceutical market due to its many applications and targeted therapeutic research using lutetium-based radiopharmaceuticals. However, lutetium-based radiopharmaceuticals currently approved by the US Food and Drug Administration (FDA) are limited to the indications of gastrointestinal cancer, pancreatic neuroendocrine cancer and metastatic castration-resistant prostate cancer. To overcome these limitations, we aimed to demonstrate the feasibility of expanding the use of lutetium-based radiopharmaceuticals by verifying the availability and therapeutic efficacy of lutetium produced in a research reactor(HANARO). In this study, we confirmed the therapeutic efficacy of lutetium by using cancer cells from different types of cancer. In addition, we selected cancer biomarkers based on characteristics common to various cancer cells and compared and evaluated the therapeutic efficacy of lutetium by regulating the expression of target genes. The results showed that modulation of cancer biomarker gene expression resulted in higher therapeutic efficacy compared to lutetium alone. In conclusion, this study verified the potential use and therapeutic efficacy of lutetium based on the production of a research reactor (HANARO), providing fundamental evidence for the development of lutetium-based radiopharmaceuticals and the expansion of their indications.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7467-7472
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• 2013

Background: Polymorphisms of genes encoding cytokines could be potential biomarkers to predict risk of gastric cancer (GC). Here, we investigated the association between the IL-6 -6331 (T/C, rs10499563) polymorphism in its promoter region and GC risk. Methods: In this case-control study of 215 GC cases and 518 non-cancer controls, the IL-6 -6331 (T/C, rs10499563) polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: Individuals with the TC or CC genotype were associated with a significantly decreased risk of GC (OR=0.710, 95%CI: 0.504-0.999, P=0.049) compared with TT wild-type carriers. Ther C allele was also associated with significantly decreased risk of GC (OR=0.715, 95%CI: 0.536-0.954, P=0.023) compared with the T allele. In the stratification analysis, TC or CC genotypes were associated with significantly decreased GC risk in subgroups of males, people older than 60, and H. pylori-positive cases. However, no significant interaction was observed for TC or CC genotypes with H. pylori infection. On stratification with the Lauren classification, TC or CC genotypes were associated with significantly decreased risk of diffuse-type GC (OR=0.497, 95%CI: 0.266-0.925, P=0.027), also in subgroups of males, people older than 60, and H. pylori-positive cases. Conclusions: The IL-6 -6331 (T/C, rs10499563) polymorphism is associated with genetic susceptibility of GC and may have the potential to predict GC risk.

• Journal of Genetic Medicine
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• 제6권1호
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• pp.1-7
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• 2009

프로모터 CpG island 과메틸화와 히스톤 변경으로 대변되는 후성유전적 변화는 거의 모든 종류의 암에서 발견되는 중요한 발암기전이다. 인간유전자의 60-70% 가량이 프로모터에 CpG islands를 가지고 있으며, 이 유전자들 중 일부가 과메틸화됨으로써 해당유전자의 발현이 차단되고, 종양억제기능이 소실되어 종양세포의 성장을 촉진하게 된다. 암에는 프로모터 CpG island 과메틸화라는 국소적 변화 이외에, 유전체 전반에 걸친 탈메틸화를 동시에 보이는 경우가 대부분인데, 이러한 유전체 저메틸화는 염색체 불안정성과 밀접한 연관관계가 있다. 국소적 과메틸화와 전반적인 저메틸화라는 이러한 상반된 DNA 메틸화 변화는 암세포뿐만 아니라 그 전단계 병변인 이 형성 병변에서도 관찰된다. 프로모터CpG island 과메틸화는 유전자 발현억제 기전으로서의 중요성뿐만 아니라 종양표지자로서의 중요성이 부각되고 있다. 즉, 정상세포에서는 관찰되지 않으면서 암세포에서만 관찰되는 프로모터 CpG island 과메틸화는 암세포의 바이오마커로서의 가치가 있으며, 이를 이용하여 체액에서 암을 진단하려는 시도들이 이루어지고, 이를 활용한 암의 분자진단방법이 개발되고 있다. 또한 이러한 DNA 메틸화는 암환자의 예후 판정이나 항암치료제의 감수성 결정 등에 활용되고 있다. 본 원고에서는 인체 암세포에서의 DNA 메틸화 변화에 관하여 소개하고자 한다.