• Title/Summary/Keyword: Genetic Factor

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Transcriptome Profiling Identifies Genes of Waterlogging-Tolerant and -Sensitive Rapeseeds Differentially Respond to Waterlogging Stress at the Flowering Stage

  • Ji-Eun Lee;Da-Hee An;Kwang-Soo Kim;Young-Lok Cha;Dong-Chil Chang
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2022.10a
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    • pp.229-229
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    • 2022
  • Rapeseed is a crop that is waterlogging sensitive, and it is necessary to breed waterlogging tolerance varieties. Our study presents the comparative transcriptome changes in two rapeseed lines, i.e., waterlogging-tolerant (tJ8634-B-30,) and - sensitive ('EMS26') lines under control and waterlogging stress treatments at the flowering stage. RNA-sequencing analysis revealed 13,279 differentially expressed genes (DEGs) for 'J8634-B-30' and 8,682 DEGs for 'EMS26' under waterlogging stress condition compared to control. Among DEGs of 'J8634-B-30', 6,818 were up-regulated and 6,461 were down-regulated. On the other hand, among the DEGs of 'EMS26', the number of down-regulated genes (5,240) were higher than that of up-regulated genes (3,442). Gene ontology enrichment analysis showed that DEGs related to glucan metabolic, cell wall, and oxidoreductase activity were significantly changed in 'J8634-B-30'. Kyoto Encyclopedia of Genes and Genomes (KEGG)-based analysis in 'J8634-B-30' identified up-regulated DEGs being involved in MAPK signaling pathways. In addition, the DEGs belonging to mechanisms responding to waterlogging stress, i.e., plant hormones, carbon metabolism, Reactive oxygen species (ROS), Nitric oxide (NO) etc. were compared in rapeseed lines. Several DEGs including ethylene-responsive transcription factor (ERF), constitutive triple response (CTR) (in ethylene signaling pathway), monodehydroascorbate Reductase (MDAR), NADPH oxidase (in ROS pathway), cytochrome c oxidase assembly protein (COX) (in NO pathway) up-regulated in 'J8634-B-30'. These outcomes provided the valuable information for further exploring the genetic mechanism of waterlogging tolerance in rapeseed.

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Identification of Cell Type-Specific Effects of DNMT3A Mutations on Relapse in Acute Myeloid Leukemia

  • Seo-Gyeong Bae;Hyeoung-Joon Kim;Mi Yeon Kim;Dennis Dong Hwan Kim;So-I Shin;Jae-Sook Ahn;Jihwan Park
    • Molecules and Cells
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    • v.46 no.10
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    • pp.611-626
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    • 2023
  • Acute myeloid leukemia (AML) is a heterogeneous disease caused by distinctive mutations in individual patients; therefore, each patient may display different cell-type compositions. Although most patients with AML achieve complete remission (CR) through intensive chemotherapy, the likelihood of relapse remains high. Several studies have attempted to characterize the genetic and cellular heterogeneity of AML; however, our understanding of the cellular heterogeneity of AML remains limited. In this study, we performed single-cell RNA sequencing (scRNAseq) of bone marrow-derived mononuclear cells obtained from same patients at different AML stages (diagnosis, CR, and relapse). We found that hematopoietic stem cells (HSCs) at diagnosis were abnormal compared to normal HSCs. By improving the detection of the DNMT3A R882 mutation with targeted scRNAseq, we identified that DNMT3A-mutant cells that mainly remained were granulocyte-monocyte progenitors (GMPs) or lymphoid-primed multipotential progenitors (LMPPs) from CR to relapse and that DNMT3A-mutant cells have gene signatures related to AML and leukemic cells. Copy number variation analysis at the single-cell level indicated that the cell type that possesses DNMT3A mutations is an important factor in AML relapse and that GMP and LMPP cells can affect relapse in patients with AML. This study advances our understanding of the role of DNMT3A in AML relapse and our approach can be applied to predict treatment outcomes.

Differential microbiota network according to colorectal cancer lymph node metastasis stages

  • Yeuni Yu;Donghyun Han;Hyomin Kim;Yun Hak Kim;Dongjun Lee
    • Journal of Genetic Medicine
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    • v.20 no.2
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    • pp.52-59
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    • 2023
  • Purpose: Colorectal cancer (CRC) is a common malignancy worldwide and the second leading cause of cancer-related deaths. In addition, lymph node metastasis in CRC is considered an important prognostic factor for predicting disease recurrence and patient survival. Recent studies demonstrated that the microbiome makes substantial contributions to tumor progression, however, there is still unknown about the microbiome associated with lymph node metastasis of CRC. Here, we first reported the microbial and tumor-infiltrating immune cell differences in CRC according to the lymph node metastasis status. Materials and Methods: Using Next Generation Sequencing data acquired from 368 individuals diagnosed with CRC (N0, 266; N1, 102), we applied the LEfSe to elucidate microbial differences. Subsequent utilization of the Kaplan-Meier survival analysis enabled the identification of particular genera exerting significant influence on patient survival outcomes. Results: We found 18 genera in the N1 group and 3 genera in the N0 group according to CRC lymph node metastasis stages. In addition, we found that the genera Crenobacter (P=0.046), Maricaulis (P=0.093), and Arsenicicoccus (P=0.035) in the N0 group and Cecembia (P=0.08) and Asanoa (P=0.088) in the N1 group were significantly associated with patient survival according to CRC lymph node metastasis stages. Further, Cecembia is highly correlated to tumor-infiltrating immune cells in lymph node metastasized CRC. Concolusion: Our study highlights that tumor-infiltrating immune cells and intratumoral microbe diversity are associated with CRC. Also, this potential microbiome-based oncology diagnostic tool warrants further exploration.

Sustainable animal agriculture in the United States and the implication in Republic of Korea

  • Inkuk Yoon;Sang-Hyon Oh;Sung Woo Kim
    • Journal of Animal Science and Technology
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    • v.66 no.2
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    • pp.279-294
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    • 2024
  • Agriculture has played a significant role in the national economy, contributing to food security, driving economic growth, and safeguarding the dietary habits of the population. Korean agriculture has been compelled to focus on intensive farming due to its limited cultivation area, excessive input costs, and the limitations of agricultural mechanization. In the Republic of Korea (R.O.K), the concept of environmentally friendly animal agriculture began to be introduced in the early 2000s. This concept ultimately aims to cultivate sustainable animal agriculture (SAA) through environmentally friendly production practices, ensuring the healthy rearing of animals to supply safe animal products. Despite the government's efforts, there are still significant challenges in implementing environmentally friendly agriculture and SAA in the R.O.K. Therefore, the objective of this review is to establish the direction that the animal agriculture sector should take in the era of climate crisis, and to develop effective strategies for SAA tailored to the current situation in the R.O.K by examining the trends in SAA in the U.S. The animal agriculture sector in the U.S. has been working towards creating a SAA system where humans, animals, and the environment can coexist through government initiatives, industry research, technological support, and individual efforts. Efforts have been made to reduce emissions like carbon, and improve factors affecting the environment such as the carbon footprint, odor, and greenhouse gases associated with animal agriculture processes for animals such as cattle and pigs. The transition of the U.S. towards SAA appears to be driven by both external goals related to addressing climate change and the primary objectives of responding to the demand for safe animal products, expanding consumption, and securing competitiveness in overseas export markets. The demand for animal welfare, organic animal products, and processed goods has been increasing in the U.S. consumer market. A major factor in the transformation of the U.S. animal agriculture sector in terms of livestock specifications is attributed to environmentally friendly practices such as high-quality feed, heat stress reduction, improvements in reproductive ability and growth period reduction, and efforts in animal genetic enhancement.

An In Silico Drug Repositioning Strategy to Identify Specific STAT-3 Inhibitors for Breast Cancer

  • Sruthy Sathish
    • Journal of Integrative Natural Science
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    • v.16 no.4
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    • pp.123-131
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    • 2023
  • Breast cancer continues to pose a substantial worldwide health challenge, thereby requiring the development of innovative strategies to discover new therapeutic interventions. Signal Transducer and Activator of Transcription 3 (STAT-3) has been identified as a significant factor in the development of several types of cancer, including breast cancer. This is primarily attributed to its diverse functions in promoting tumour formation and conferring resistance to therapeutic interventions. This study presents an in silico drug repositioning approach that focuses on identifying specific inhibitors of STAT-3 for the purpose of treating breast cancer. We initially examined the structural and functional attributes of STAT-3, thereby elucidating its crucial involvement in cellular signalling cascades. A comprehensive virtual screening was performed on a diverse collection of drugs that have been approved by the FDA from zinc15 database. Various computational techniques, including molecular docking, cross docking, and cDFT analysis, were utilised in order to prioritise potential candidates. This prioritisation was based on their predicted binding energies and outer molecular orbital reactivity. The findings of our study have unveiled a Dihydroergotamine and Paritaprevir that have been approved by the FDA and exhibit considerable promise as selective inhibitors of STAT-3. In conclusion, the utilisation of our in silico drug repositioning approach presents a prompt and economically efficient method for the identification of potential compounds that warrant subsequent experimental validation as selective STAT-3 inhibitors in the context of breast cancer. The present study highlights the considerable potential of employing computational strategies to expedite the drug discovery process. Moreover, it provides valuable insights into novel avenues for targeted therapeutic interventions in the context of breast cancer treatment.

Unveiling Immunomodulatory Effects of Euglena gracilis in Immunosuppressed Mice: Transcriptome and Pathway Analysis

  • Seon Ha Jo;Kyeong Ah Jo;Soo-yeon Park;Ji Yeon Kim
    • Journal of Microbiology and Biotechnology
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    • v.34 no.4
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    • pp.880-890
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    • 2024
  • The immunomodulatory effects of Euglena gracilis (Euglena) and its bioactive component, β-1,3-glucan (paramylon), have been clarified through various studies. However, the detailed mechanisms of the immune regulation remain to be elucidated. This study was designed not only to investigate the immunomodulatory effects but also to determine the genetic mechanisms of Euglena and β-glucan in cyclophosphamide (CCP)-induced immunosuppressed mice. The animals were orally administered saline, Euglena (800 mg/kg B.W.) or β-glucan (400 mg/kg B.W.) for 19 days, and CCP (80 mg/kg B.W.) was subsequently administered to induce immunosuppression in the mice. The mice exhibited significant decreases in body weight, organ weight, and the spleen index. However, there were significant improvements in the spleen weight and the spleen index in CCP-induced mice after the oral administration of Euglena and β-glucan. Transcriptome analysis of the splenocytes revealed immune-related differentially expressed genes (DEGs) regulated in the Euglena- and β-glucantreated groups. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that pathways related with interleukin (IL)-17 and cAMP play significant roles in regulating T cells, B cells, and inflammatory cytokines. Additionally, Ptgs2, a major inflammatory factor, was exclusively expressed in the Euglena-treated group, suggesting that Euglena's beneficial components, such as carotenoids, could regulate these genes by influencing immune lymphocytes and inflammatory cytokines in CCP-induced mice. This study validated the immunomodulatory effects of Euglena and highlighted its underlying mechanisms, suggesting a positive contribution to the determination of phenotypes associated with immune-related diseases and the research and development of immunotherapies.

Effect of S100A8 and S100A9 on expressions of cytokine and skin barrier protein in human keratinocytes

  • MUN JEONG KIM;MI AE IM;JI‑SOOK LEE;JI YOUNG MUN;DA HYE KIM;AYOUNG GU;IN SIK KIM
    • Molecular Medicine Reports
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    • v.20 no.3
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    • pp.2476-2483
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    • 2019
  • Atopic dermatitis (AD ) is an inflammatory skin disorder caused by immunological dysregulation and genetic factors. Whether the expression levels of cytokine and skin barrier protein were altered by S100 calcium binding protein A8 (S100A8) and S100A9 in human keratinocytic HaCaT cells was examined in the present study. Alterations of cytokine expression were examined by ELI SA following treatment with S100A8/9 and various signal protein-specific inhibitors. Activation of the mitogen activated protein kinase (MAPK) pathway and nuclear factor (NF)-κB was evaluated by using western blotting and an NF-κB activity test, respectively. The expression levels of interleukin (IL )-6, IL- 8 and monocyte chemoattractant protein-1 increased following treatment with S100A8 and S100A9, and the increase was significantly blocked by specific signaling pathway inhibitors, including toll-like receptor 4 inhibitor (TLR 4i), rottlerin, PD98059, SB203580 and BAY-11-7085. Extracellular signal-regulated kinase (ER K) and p38 MAPK pathways were activated in a time-dependent manner following treatment with S100A8 and S100A9. Phosphorylation of ER K and p38 MAPK were blocked by TLR 4i and rottlerin. S100A8 and S100A9 induced translocation of NF-κB in a time-dependent manner, and the activation of NF-κB was inhibited by TLR 4i, rottlerin, PD98059 and SB203580. In addition, S100A8 and S100A9 decreased the expression of skin barrier proteins, filaggrin and loricrin. These results may help to elucidate the pathogenic mechanisms of AD and develop clinical strategies for controlling AD.

Impaired Osteogenesis in Human Induced Pluripotent Stem Cells with Acetaldehyde Dehydrogenase 2 Mutations

  • Jooyoung Lim;Heeju Han;Se In Jung;Yeri Alice Rim;Ji Hyeon Ju
    • International Journal of Stem Cells
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    • v.17 no.3
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    • pp.284-297
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    • 2024
  • Acetaldehyde dehydrogenase 2 (ALDH2) is the second enzyme involved in the breakdown of acetaldehyde into acetic acid during the process of alcohol metabolism. Roughly 40% of East Asians carry one or two ALDH2*2 alleles, and the presence of ALDH2 genetic mutations in individuals may affect the bone remodeling cycle owing to accumulation of acetaldehyde in the body. In this study, we investigated the effects of ALDH2 mutations on bone remodeling. In this study, we examined the effects of ALDH2 polymorphisms on in vitro osteogensis using human induced pluripotent stem cells (hiPSCs). We differentiated wild-type (ALDH2*1/*1-) and ALDH2*1/*2-genotyped hiPSCs into osteoblasts (OBs) and confirmed their OB characteristics. Acetaldehyde was administered to confirm the impact caused by the mutation during OB differentiation. Calcium deposits formed during osteogenesis were significantly decreased in ALDH2*1/*2 OBs. The expression of osteogenic markers were also decreased in acetaldehyde-treated OBs differentiated from the ALDH2*1/*2 hiPSCs. Furthermore, the impact of ALDH2 polymorphism and acetaldehyde-induced stress on inflammatory factors such as 4-hydroxynonenal and tumor necrosis factor α was confirmed. Our findings suggest that individuals with ALDH2 deficiency may face challenges in acetaldehyde breakdown, rendering them susceptible to disturbances in normal bone remodeling therefore, caution should be exercised regarding alcohol consumption. In this proof-of-concept study, we were able to suggest these findings as a result of a disease-in-a-dish concept using hiPSCs derived from individuals bearing a certain mutation. This study also shows the potential of patient-derived hiPSCs for disease modeling with a specific condition.

Recovery of ovarian activity and uterine involution in postpartum primiparous Hanwoo cow

  • Yonghwan Kim;Myungsun Park;Jeong Il Won;Shil Jin;Hyoun Ju Kim;Eunju Kim;Sung Woo Kim;Sang-Rae Cho;Seunghoon Lee;Youl-Chang Baek;Bongki Kim;Sung-Sik Kang
    • Journal of Animal Reproduction and Biotechnology
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    • v.39 no.3
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    • pp.201-211
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    • 2024
  • Background: Hanwoo cattle farmers aim to improve calf production and reproductive efficiency. Recovery of the reproductive tract postpartum is a critical factor influencing the postpartum period and conception of breeding cows. This study aimed to precisely analyze the recovery process of the reproductive tract in primiparous Hanwoo postpartum and to establish recovery criteria. Methods: Ten primiparous Hanwoo cows were used in this study. After parturition, estrus was examined daily using visual observations and estrus detection patches. Ovarian recovery, cervical diameter, and uterine horn diameter were examined using ultrasonography four times per week. Results: The analysis revealed that the first estrus occurred at 19.1 ± 6.5 days postpartum, the first ovulation at 27.1 ± 4.5 days, and the first normal estrus cycle at 39.2 ± 6.4 days. The ovulation rate during the first estrus was 40%. A normal estrus cycle occurred in 11.1% of patients at the first ovulation. The cervix diameter recovered to 42.0 ± 3.5 mm and the uterine horn diameter to 34.4 ± 7.1 mm by 24 days postpartum, with the difference in uterine horn diameter recovering to 2.6 ± 1.2 mm by 31 days postpartum. Conclusions: This study can aid in determining the optimal breeding time for postpartum primiparous Hanwoo cow and provide foundational data for Hanwoo breeding studies.

Characterization of Hrq1-Rad14 Interaction in Saccharomyces cerevisiae (효모에서 Hrq1과 Rad14의 상호작용에 대한 연구)

  • Min, Moon-Hee;Kim, Min-Ji;Choi, You-Jin;You, Min-Ju;Kim, Uy-Ra;An, Hyo-Bin;Kim, Chae-Hyun;Kwon, Chae-Yeon;Bae, Sung-Ho
    • Korean Journal of Microbiology
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    • v.50 no.2
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    • pp.95-100
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    • 2014
  • Hrq1 is a novel member of RecQ helicase family, found in fungal genomes by bioinformatics analyses. It is most homologous to human RECQL4 and recent genetic and biochemical studies suggested that it may play roles in the maintenance of genome stability. In this study, we investigated yeast two-hybrid interactions between Hrq1 and the yeast genes homologous to the human genes that are known to interact with RECQL4. Among the 11 genes tested, Rad14, a nucleotide excision repair (NER) factor, was found to interact with Hrq1. In addition, pull-down assay with the purified proteins revealed direct protein-protein interaction between Hrq1 and Rad14. The yeast two-hybrid interaction was enhanced by the DNA damage induced by 4-nitroquinoline-1-oxide, which was dependent on the presence of Rad4, a key NER factor. These results suggest that Hrq1 may function in NER through interaction with Rad14.