• Title/Summary/Keyword: Molecular Characteristics

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The Role of CYP2B6*6 Gene Polymorphisms in 3,5,6-Trichloro-2-pyridinol Levels as a Biomarker of Chlorpyrifos Toxicity Among Indonesian Farmers

  • Liem, Jen Fuk;Suryandari, Dwi A.;Malik, Safarina G.;Mansyur, Muchtaruddin;Soemarko, Dewi S.;Kekalih, Aria;Subekti, Imam;Suyatna, Franciscus D.;Pangaribuan, Bertha
    • Journal of Preventive Medicine and Public Health
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    • v.55 no.3
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    • pp.280-288
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    • 2022
  • Objectives: One of the most widely used pesticides today is chlorpyrifos (CPF). Cytochrome P450 (CYP)2B6, the most prominent catalyst in CPF bioactivation, is highly polymorphic. The objective of our study was to evaluate the role of CYP2B6*6, which contains both 516G>T and 785A>G polymorphisms, in CPF toxicity, as represented by the concentration of 3,5,6-trichloro-2-pyridinol (TCPy), among vegetable farmers in Central Java, Indonesia, where CPF has been commonly used. Methods: A cross-sectional study was conducted among 132 vegetable farmers. Individual socio-demographic and occupational characteristics, as determinants of TCPy levels, were obtained using a structured interviewer-administered questionnaire and subsequently used to estimate the cumulative exposure level (CEL). TCPy levels were detected with liquid chromatography-mass spectrometry. CYP2B6*6 gene polymorphisms were analyzed using a TaqMan® SNP Genotyping Assay and Sanger sequencing. Linear regression analysis was performed to analyze the association between TCPy, as a biomarker of CPF exposure, and its determinants. Results: The prevalence of CYP2B6*6 polymorphisms was 31% for *1/*1, 51% for *1/*6, and 18% for *6/*6. TCPy concentrations were higher among participants with CYP2B6*1/*1 than among those with *1/*6 or *6/*6 genotypes. CYP2B6*6 gene polymorphisms, smoking, CEL, body mass index, and spraying time were retained in the final linear regression model as determinants of TCPy. Conclusions: The results suggest that CYP2B6*6 gene polymorphisms may play an important role in influencing susceptibility to CPF exposure. CYP2B6*6 gene polymorphisms together with CEL, smoking habits, body mass index, and spraying time were the determinants of urinary TCPy concentrations, as a biomarker of CPF toxicity.

Deciphering the DNA methylation landscape of colorectal cancer in a Korean cohort

  • Seok-Byung Lim;Soobok Joe;Hyo-Ju Kim;Jong Lyul Lee;In Ja Park;Yong Sik Yoon;Chan Wook Kim;Jong-Hwan Kim;Sangok Kim;Jin-Young Lee;Hyeran Shim;Hoang Bao Khanh Chu;Sheehyun Cho;Jisun Kang;Si-Cho Kim;Hong Seok Lee;Young-Joon Kim;Seon-Young Kim;Chang Sik Yu
    • BMB Reports
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    • v.56 no.10
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    • pp.569-574
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    • 2023
  • Aberrant DNA methylation plays a pivotal role in the onset and progression of colorectal cancer (CRC), a disease with high incidence and mortality rates in Korea. Several CRC-associated diagnostic and prognostic methylation markers have been identified; however, due to a lack of comprehensive clinical and methylome data, these markers have not been validated in the Korean population. Therefore, in this study, we aimed to obtain the CRC methylation profile using 172 tumors and 128 adjacent normal colon tissues of Korean patients with CRC. Based on the comparative methylome analysis, we found that hypermethylated positions in the tumor were predominantly concentrated in CpG islands and promoter regions, whereas hypomethylated positions were largely found in the open-sea region, notably distant from the CpG islands. In addition, we stratified patients by applying the CpG island methylator phenotype (CIMP) to the tumor methylome data. This stratification validated previous clinicopathological implications, as tumors with high CIMP signatures were significantly correlated with the proximal colon, higher prevalence of microsatellite instability status, and MLH1 promoter methylation. In conclusion, our extensive methylome analysis and the accompanying dataset offers valuable insights into the utilization of CRC-associated methylation markers in Korean patients, potentially improving CRC diagnosis and prognosis. Furthermore, this study serves as a solid foundation for further investigations into personalized and ethnicity-specific CRC treatments.

A Study on Characteristics of Polymer Organic Hard Mask Synthesis (고분자 유기하드마스크 합성에 따른 특성에 관한 연구)

  • Woo-Sik Lee
    • The Journal of Korea Institute of Information, Electronics, and Communication Technology
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    • v.16 no.5
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    • pp.217-222
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    • 2023
  • The purpose of this paper was to synthesize a polymer organic hard mask that simplifies the manufacturing process, reduces process time significantly, and thereby lowers manufacturing costs. The results of measuring residual metals through vapor refining showed that 9-Naphthalen-1-ylcarbazole(9-NC) measured 101.75ppb in the 4th zone, 2-Naphthol (2-NA) measured 306.98ppb in the 5th zone, and 9-Fluorenone(9-F) measured between 129.05ppb across the 4th and 5th zones. After passing through a filtration system, the synthesized organic hard mask measured residual metals in the range of 9 to 7ppb. Additionally, the thermal analysis indicated a decrease of 2.78%, a molecular weight of 942, carbon content of 89.74%, and a yield of 72.4%. The etching rate was measured at an average of 18.22Å/s, and the coating thickness deviation was averaged at 1.19. For particle sizes below 0.2㎛ in the organic hard mask, no particles were observed. By varying the coating speed at 1,000, 1,500, and 1,800rpm and measuring the resulting coating thickness, the shrinkage rate ranged from 17.9% to 20.8%. The coating results demonstrated excellent adhesion to SiON, and it was evident that the organic hard mask was uniformly applied.

Fruit Morphology, Citrulline, and Arginine Levels in Diverse Watermelon (Citrullus lanatus) Germplasm Collections

  • Awraris Derbie Assefa;On-Sook Hur;Na-Young Ro;Jae-Eun Lee;Ae-Jin Hwang;Bit-Sam Kim;Ju-hee Rhee;Jung Yoon Yi;Ji Hyun Kim;Ho-Sun Lee;Jung-Sook Sung;Myung-Kon Kim;Jae-Jong Noh
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2020.08a
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    • pp.33-33
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    • 2020
  • Watermelon (Citrullus lanatus) is a non-seasonal, economically important, cucurbit cultivated throughout the world with Asia as a continent contributing the most. As part of the effort in diversifying watermelon genetic resources in the already cultivated group, this study was devoted to providing baseline data on morphological quality traits and health-beneficial phytonutrients of watermelon germplasm collections, thereby promoting watermelon research and cultivation programs. To this end, we reported morphological traits, citrulline, and arginine levels of watermelon genetic resources obtained from the gene bank of Agrobiodiversity Center, Republic of Korea, and discussed the relationship between each other. Diverse characteristics were observed among many of the traits. But, most of the genetic resources (>90%) were either red or pink-fleshed. Korean origin fruits contained intermediate levels of soluble solid content (SSC) while The USA, Russian, Tajikistan, Turkmenistan, Taiwan, and Uruguay originated had generally the highest levels of soluble solids. The citrulline and arginine contents using HPLC method were ranged from 6.9 to 52.1 mg/g (average, 27.3 mg/g) and 1.8 to 21.3 mg/g (average, 9.8 mg/g), respectively. The citrulline content determined using Citrulline Assay Kit was ranged from 6.5 to 42.8 mg/g (average, 27.0 mg/g). Resources with high citrulline and arginine levels contained low SSC. Whereas, red- and pink-colored flesh samples had less citrulline compared to yellow and orange. In addition to the profiling of morphological characters and phytonutrients, molecular marker characterization and identification of sources of resistance to diseases and pests are recommended for a more complete diversity analysis of watermelon genetic resources.

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CD5 Expression Dynamically Changes During the Differentiation of Human CD8+ T Cells Predicting Clinical Response to Immunotherapy

  • Young Ju Kim;Kyung Na Rho;Saei Jeong;Gil-Woo Lee;Hee-Ok Kim;Hyun-Ju Cho;Woo Kyun Bae;In-Jae Oh;Sung-Woo Lee;Jae-Ho Cho
    • IMMUNE NETWORK
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    • v.23 no.4
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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.

DNA Mutation Pattern of gyrA and gyrB Genes according to the SCCmec Subtype of Quinolone-resistant Staphylococcus aureus Isolates from Blood Culture (혈액배양에서 분리된 Fluoroquinolone계 약제 내성 황색포도알균의 SCCmec 아형에 따른 gyrA와 gyrB 유전자에서의 DNA 돌연변이 양상)

  • Inwon HWANG;Sang-Ha KIM;Taewon JUNG;Young-Kwon KIM;Sunghyun KIM
    • Korean Journal of Clinical Laboratory Science
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    • v.56 no.2
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    • pp.115-124
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    • 2024
  • The emergence and spread of Staphylococcus aureus, which is resistant to quinolone antibacterial agents, has made it difficult to treat infectious diseases. Accordingly, this study examined the molecular epidemiological characteristics of quinolone-resistant S. aureus (QRSA) to obtain helpful data for treatment. Mutations in mecA and SCCmec typing, gyrA, and gyrB genes were investigated for QRSA strains isolated from the blood culture specimens at a general hospital in Daejeon Metropolitan City. The ciprofloxacin-resistant strains in SCCmec typing were II (44 strains, 73%), IVa (five strains, 8%), III, and V (one strain, 2%); the non-typeable strains (11 strains, 18%), and levofloxacin (LVX) and moxifloxacin (MXF) strains were II (44 strains, 73%), IVa (five strains, 8%), III, and V (one strain, 2%); the non-typeable strains were 10 (17%). In both gyrA and gyrB regions, there were 58 mutations, or 96.7%. In LVX, there were 56 mutations or 93.3%, and in MXF, there were 57 mutations or 95%. Twelve mutations, six mutations each in gyrA and gyrB, were identified for the QRSA strain. The resistance rate for the quinolone antibiotics of QRSA studied was approximately 98%, and 12 mutations, six each in gyrA and gyrB, were identified in the QRSA strain. Therefore, the rational use of antibiotics needs to be improved.

Identification of relevant differential genes to the divergent development of pectoral muscle in ducks by transcriptomic analysis

  • Fan Li;Zongliang He;Yinglin Lu;Jing Zhou;Heng Cao;Xingyu Zhang;Hongjie Ji;Kunpeng Lv;Debing Yu;Minli Yu
    • Animal Bioscience
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    • v.37 no.8
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    • pp.1345-1354
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    • 2024
  • Objective: The objective of this study was to identify candidate genes that play important roles in skeletal muscle development in ducks. Methods: In this study, we investigated the transcriptional sequencing of embryonic pectoral muscles from two specialized lines: Liancheng white ducks (female) and Cherry valley ducks (male) hybrid Line A (LCA) and Line C (LCC) ducks. In addition, prediction of target genes for the differentially expressed mRNAs was conducted and the enriched gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes signaling pathways were further analyzed. Finally, a protein-to-protein interaction network was analyzed by using the target genes to gain insights into their potential functional association. Results: A total of 1,428 differentially expressed genes (DEGs) with 762 being up-regulated genes and 666 being down-regulated genes in pectoral muscle of LCA and LCC ducks identified by RNA-seq (p<0.05). Meanwhile, 23 GO terms in the down-regulated genes and 75 GO terms in up-regulated genes were significantly enriched (p<0.05). Furthermore, the top 5 most enriched pathways were ECM-receptor interaction, fatty acid degradation, pyruvate degradation, PPAR signaling pathway, and glycolysis/gluconeogenesis. Finally, the candidate genes including integrin b3 (Itgb3), pyruvate kinase M1/2 (Pkm), insulin-like growth factor 1 (Igf1), glucose-6-phosphate isomerase (Gpi), GABA type A receptor-associated protein-like 1 (Gabarapl1), and thyroid hormone receptor beta (Thrb) showed the most expression difference, and then were selected to verification by quantitative real-time polymerase chain reaction (qRT-PCR). The result of qRT-PCR was consistent with that of transcriptome sequencing. Conclusion: This study provided information of molecular mechanisms underlying the developmental differences in skeletal muscles between specialized duck lines.

Comparative analysis of liver transcriptome reveals adaptive responses to hypoxia environmental condition in Tibetan chicken

  • Yongqing Cao;Tao Zeng;Wei Han;Xueying Ma;Tiantian Gu;Li Chen;Yong Tian;Wenwu Xu;Jianmei Yin;Guohui Li;Lizhi Lu;Shuangbao Gun
    • Animal Bioscience
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    • v.37 no.1
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    • pp.28-38
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    • 2024
  • Objective: Tibetan chickens, which have unique adaptations to extreme high-altitude environments, exhibit phenotypic and physiological characteristics that are distinct from those of lowland chickens. However, the mechanisms underlying hypoxic adaptation in the liver of chickens remain unknown. Methods: RNA-sequencing (RNA-Seq) technology was used to assess the differentially expressed genes (DEGs) involved in hypoxia adaptation in highland chickens (native Tibetan chicken [HT]) and lowland chickens (Langshan chicken [LS], Beijing You chicken [BJ], Qingyuan Partridge chicken [QY], and Chahua chicken [CH]). Results: A total of 352 co-DEGs were specifically screened between HT and four native lowland chicken breeds. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses indicated that these co-DEGs were widely involved in lipid metabolism processes, such as the peroxisome proliferator-activated receptors (PPAR) signaling pathway, fatty acid degradation, fatty acid metabolism and fatty acid biosynthesis. To further determine the relationship from the 352 co-DEGs, protein-protein interaction network was carried out and identified eight genes (ACSL1, CPT1A, ACOX1, PPARC1A, SCD, ACSBG2, ACACA, and FASN) as the potential regulating genes that are responsible for the altitude difference between the HT and other four lowland chicken breeds. Conclusion: This study provides novel insights into the molecular mechanisms regulating hypoxia adaptation via lipid metabolism in Tibetan chickens and other highland animals.

Prognostic Value of Dynamic Contrast-Enhanced MRI-Derived Pharmacokinetic Variables in Glioblastoma Patients: Analysis of Contrast-Enhancing Lesions and Non-Enhancing T2 High-Signal Intensity Lesions

  • Yeonah Kang;Eun Kyoung Hong;Jung Hyo Rhim;Roh-Eul Yoo;Koung Mi Kang;Tae Jin Yun;Ji-Hoon Kim;Chul-Ho Sohn;Sun-Won Park;Seung Hong Choi
    • Korean Journal of Radiology
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    • v.21 no.6
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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.

Human Understanding is Expected of the Physician: Proposing a Model of Disease Development (의사에게 요구되는 인간이해를 통합한 질병발생모델의 제안)

  • Sang-Heum Park;Samel Park;Jin Young Kim;Hyeon Ah Lee;Sang Mi Lee;Tae Hoon Lee;Sang Byung Bae;Sung Hae Chang;Si Hyong Jang;Sung Wan Chun;Jong Ho Moon
    • The Korean Journal of Medicine
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    • v.99 no.2
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    • pp.84-95
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    • 2024
  • In Harrison's Principles of Internal Medicine, human understanding is emphasized as one of three necessary characteristics that a physician must have. Inflammation, which is caused by inflammatory inducers (inf-ids), is a fundamental feature of disease at the cellular and molecular levels. Inflammation protects the body, but excessive or prolonged inflammation can be damaging and can cause disease. Humans are repeatedly exposed to external and internal environmental factors that generate inf-ids throughout their lives. External environmental factors include microbial and non-microbial inf-ids, as well as stressors that inevitably arise during social interactions. Internal environmental factors include the adaptive physiological response that is present from birth. Inf-ids may also be produced by the four-step habit loop, which consists of a cue (e.g., stressor), emotions, routine act (adaptive response), and a reward. Immune cells in the circulatory system and in tissues may have positive and negative effects in inflammatory responses. However, low-grade inflammation may be difficult to detect. We propose a model of disease development that integrates external and internal environmental factors from the perspective of human understanding.