• Journal of The Korean Society of Grassland and Forage Science
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• v.37 no.3
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• pp.231-236
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• 2017

Salt stress is one of the most limiting factors that reduce plant growth, development and yield. However, identification of salt-inducible genes is an initial step for understanding the adaptive response of plants to salt stress. In this study, we used an annealing control primer (ACP) based GeneFishing technique to identify differentially expressed genes (DEGs) in Italian ryegrass seedlings under salt stress. Ten-day-old seedlings were exposed to 100 mM NaCl for 6 h. Using 60 ACPs, a total 8 up-regulated genes were identified and sequenced. We identified several promising genes encoding alpha-glactosidase b, light harvesting chlorophyll a/b binding protein, metallothionein-like protein 3B-like, translation factor SUI, translation initiation factor eIF1, glyceraldehyde-3-phosphate dehydrogenase 2 and elongation factor 1-alpha. These genes were mostly involved in plant development, signaling, ROS detoxification and salt acclimation. However, this study provides new molecular information of several genes to understand the salt stress response. These genes would be useful for the enhancement of salt stress tolerance in plants.

• Nutrition Research and Practice
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• v.10 no.1
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• pp.42-48
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• 2016

BACKGROUND/OBJECTIVES: Seaweeds have been reported to have various health beneficial effects. In this study, we investigated the potential anti-obesity and anti-inflammatory effects of four types of domestic brown seaweeds in a high-fat diet-induced obese mouse model and bone marrow-derived macrophages (BMDM). MATERIALS/METHODS: Male C57BL/6N mice were fed low-fat diet (LFD), high-fat diet (HFD) or HFD containing Undaria Pinnatifida, HFD containing Laminaria Japonica (LJ), HFD containing Sargassum Fulvellum, or HFD containing Hizikia Fusiforme (HF) for 16 weeks. RESULTS: Brown seaweed supplementation did not affect long-term HFD-associated changes in body weight or adiposity, although mice fed HFD + LJ or HFD + HF gained slightly less body weight compared with those fed HFD at the beginning of feeding. Despite being obese, mice fed HFD + LJ appeared to show improved insulin sensitivity compared to mice fed HFD. Consistently, we observed significantly reduced blood glucose concentrations in mice fed HFD + LJ compared with those of mice fed HFD. Although no significant differences in adipocyte size were detected among the HFD-fed groups, consumption of seaweeds decreased formation of HFD-induced crown-like structures in gonadal adipose tissue as well as plasma inflammatory cytokines. BMDM from mice fed HFDs with seaweeds showed differential regulation of pro-inflammatory cytokines such as IL-$1{\beta}$ and IL-6 compared with BMDM from mice fed HFD by LPS stimulation. CONCLUSION: Although seaweed consumption did not prevent long-term HFD-induced obesity in C57BL/6N mice, it reduced insulin resistance (IR) and circulation of pro-inflammatory cytokines. Therefore, seaweeds may ameliorate systemic inflammation and IR in obesity partially due to inhibition of inflammatory signaling in adipose tissue cells as well as bone marrow-derived immune cells.

• Korean Journal of Breeding Science
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• v.43 no.1
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• pp.1-13
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• 2011

Low temperature stress is one of the major negative factors affecting vegetative and reproductive growth of rice. To better understand responses of rice plants to low temperature we analyzed transcriptome expression patterns in glumous flower of cold-tolerant japonica rice variety, Stejaree45, and cold-susceptible variety, HR19621-AC6 at booting stage under cold water irrigation. A total of 2,411 probes were differentially expressed by low temperature in glumous flowers of the two varieties. Some important genes involved in hormone biosynthesis showed variety-specific regulation. Expression of GA20ox3 and GA2ox, among the genes involved in GA biosynthesis, was regulated differentially in the two varieties. Among the genes involved in IAA biosynthesis, YUCCA1 and TAA1:1 showed variety-specific regulation. Among the genes involved in cytokinin biosynthsis and signaling, expression of LOG, HK1 and HK3 was significantly down-regulated only in the cold-susceptible variety. Among the genes involved in ABA biosynthesis, NSY and AAO3 were down-regulated only in the cold-tolerant variety. In general, genes involved in GA, IAA and cytokinin biosynthesis responded to cold temperature in such a way that capacity of those bioactive hormones is maintained at relatively higher levels under cold temperature in the cold-tolerant variety, which can help minimize cold stress imposed to developing reproductive organs in the cold-tolerant variety.

• Biomolecules & Therapeutics
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• v.27 no.3
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• pp.302-310
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• 2019

Melanoma cells have been shown to respond to BRAF inhibitors; however, intrinsic and acquired resistance limits their clinical application. In this study, we performed RNA-Seq analysis with BRAF inhibitor-sensitive (A375P) and -resistant (A375P/Mdr with acquired resistance and SK-MEL-2 with intrinsic resistance) melanoma cell lines, to reveal the genes and pathways potentially involved in intrinsic and acquired resistance to BRAF inhibitors. A total of 546 differentially expressed genes (DEGs), including 239 up-regulated and 307 down-regulated genes, were identified in both intrinsic and acquired resistant cells. Gene ontology (GO) analysis revealed that the top 10 biological processes associated with these genes included angiogenesis, immune response, cell adhesion, antigen processing and presentation, extracellular matrix organization, osteoblast differentiation, collagen catabolic process, viral entry into host cell, cell migration, and positive regulation of protein kinase B signaling. In addition, using the PAN-THER GO classification system, we showed that the highest enriched GOs targeted by the 546 DEGs were responses to cellular processes (ontology: biological process), binding (ontology: molecular function), and cell subcellular localization (ontology: cellular component). Ingenuity pathway analysis (IPA) network analysis showed a network that was common to two BRAF inhibitorresistant cells. Taken together, the present study may provide a useful platform to further reveal biological processes associated with BRAF inhibitor resistance, and present areas for therapeutic tool development to overcome BRAF inhibitor resistance.

• Clinical and Experimental Pediatrics
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• v.64 no.7
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• pp.355-363
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• 2021

Background: Nephrotic syndrome (NS) is a common renal disorder in children attributed to podocyte injury. However, children with the same diagnosis have markedly variable treatment responses, clinical courses, and outcomes, suggesting molecular heterogeneity. Purpose: This study aimed to explore the molecular responses of podocytes to nephrotic plasma to identify specific genes and signaling pathways differentiating various clinical NS groups as well as biological processes that drive injury in normal podocytes. Methods: Transcriptome profiles from immortalized human podocyte cell line exposed to the plasma of 8 subjects (steroid-sensitive nephrotic syndrome [SSNS], n=4; steroid-resistant nephrotic syndrome [SRNS], n=2; and healthy adult individuals [control], n=2) were generated using microarray analysis. Results: Unsupervised hierarchical clustering of global gene expression data was broadly correlated with the clinical classification of NS. Differential gene expression (DGE) analysis of diseased groups (SSNS or SRNS) versus healthy controls identified 105 genes (58 up-regulated, 47 down-regulated) in SSNS and 139 genes (78 up-regulated, 61 down-regulated) in SRNS with 55 common to SSNS and SRNS, while the rest were unique (50 in SSNS, 84 genes in SRNS). Pathway analysis of the significant (P≤0.05, -1≤ log2 FC ≥1) differentially expressed genes identified the transforming growth factor-β and Janus kinase-signal transducer and activator of transcription pathways to be involved in both SSNS and SRNS. DGE analysis of SSNS versus SRNS identified 2,350 genes with values of P≤0.05, and a heatmap of corresponding expression values of these genes in each subject showed clear differences in SSNS and SRNS. Conclusion: Our study observations indicate that, although podocyte injury follows similar pathways in different clinical subgroups, the pathways are modulated differently as evidenced by the heatmap. Such transcriptome profiling with a larger cohort can stratify patients into intrinsic subtypes and provide insight into the molecular mechanisms of podocyte injury.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.175-183
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• 2021

The mitogen-activated protein kinase (MAPK) pathway controls intestinal epithelial barrier permeability by regulating tight junctions (TJs) and epithelial cells damage. Heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal epithelial barrier function, but the molecular mechanism is not yet clarified. MAPK activation and barrier permeability were studied using monolayers of Caco-2 cells treated with tissue necrosis factor α (TNF-α) transfected with FUGW-HO-1 or pLKO.1-sh-HO-1 plasmid. Intestinal mucosal barrier permeability and MAPK activation were also investigated using carbon tetrachloride (CCl4) administration with CoPP (a HO-1 inducer), ZnPP (a HO-1 inhibitor), CO releasing molecule 2 (CORM-2), or inactived-CORM-2-treated wild-type mice and mice with HO-1 deficiency in intestinal epithelial cells. TNF-α increased epithelial TJ disruption and cleaved caspase-3 expression, induced ERK, p38, and JNK phosphorylation. In addition, HO-1 blocked TNF-α-induced increase in epithelial TJs disruption, cleaved caspase-3 expression, as well as ERK, p38, and JNK phosphorylation in an HO-1-dependent manner. CoPP and CORM-2 directly ameliorated intestinal mucosal injury, attenuated TJ disruption and cleaved caspase-3 expression, and inhibited epithelial ERK, p38, and JNK phosphorylation after chronic CCl4 injection. Conversely, ZnPP completely reversed these effects. Furthermore, mice with intestinal epithelial HO-1 deficient exhibited a robust increase in mucosal TJs disruption, cleaved caspase-3 expression, and MAPKs activation as compared to the control group mice. These data demonstrated that HO-1-dependent MAPK signaling inhibition preserves the intestinal mucosal barrier integrity by abrogating TJ dysregulation and epithelial cell damage. The differential targeting of gut HO-1-MAPK axis leads to improved intestinal disease therapy.

• Journal of Animal Science and Technology
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• v.64 no.4
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• pp.752-769
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• 2022

Wheat gluten is an increasingly common ingredient in poultry diets but its impact on the small intestine in chicken is not fully understood. This study aimed to identify effects of high-gluten diets on chicken small intestines and the variation of their associated transcriptional responses by age. A total of 120 broilers (Ross Strain) were used to perform two animal experiments consisting of two gluten inclusion levels (0% or 25%) by bird's age (1 week or 4 weeks). Transcriptomics and histochemical techniques were employed to study the effect of gluten on their duodenal mucosa using randomly selected 12 broilers (3 chicks per group). A reduction in feed intake and body weight gain was found in the broilers fed a high-gluten containing diet at both ages. Histochemical photomicrographs showed a reduced villus height to crypt depth ratio in the duodenum of gluten-fed broilers at 1 week. We found mainly a significant effect on the gene expression of duodenal mucosa in gluten-fed broilers at 1 week (289 differentially expressed genes [DEGs]). Pathway analyses revealed that the significant DEGs were mainly involved in ribosome, oxidative phosphorylation, and peroxisome proliferator-activated receptor (PPAR) signaling pathways. These pathways are involved in ribosome protein biogenesis, oxidative phosphorylation and fatty acid metabolism, respectively. Our results suggest a pattern of differential gene expression in these pathways that can be linked to chronic inflammation, suppression of cell proliferation, cell cycle arrest and apoptosis. And via such a mode of action, high-gluten inclusion levels in poultry diets could lead to the observed retardation of villi development in the duodenal mucosa of young broiler chicken.

• Journal of Ginseng Research
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• v.47 no.1
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• pp.133-143
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• 2023

Background: Past studies suggested that ginseng extracts and ginseng-derived molecules exerted significant regulatory effects on skin. However, no reports have described the effects of ginseng-derived nanoparticles (GDNPs) on skin cell proliferation and wound healing. In this study, we investigated whether GDNPs regulate the proliferation of skin cells and promote wound healing in a mouse model. Methods: GDNPs were separated and purified via differential centrifugation and sucrose/D2O gradient ultracentrifugation. GDNP uptake, cell proliferation and cell cycle progression were measured by confocal microscopy, CCK-8 assay and flow cytometry, respectively. Cell migration and angiogenic effects were assessed by the wound scratch assay and tube formation assay, respectively. ELISA was used to detect extracellular matrix secretion. The relevant signaling pathway was confirmed by western blotting. The effects of GDNPs on skin wound healing were assessed by wound observation, HE staining, and western blotting. Results: GDNPs possessed the essential features of exosomes, and they were accumulated by skin cells. Treatment with GDNPs notably enhanced the proliferation of HaCaT, BJ and HUVECs. GDNPs also enhanced the migration in HaCaT cells and HUVECs and angiogenesis in HUVECs. GDNPs increased the secretion of MMP-1, fibronectin-1, elastin-1, and COL1A1 in all three cell lines. GDNPs regulated cell proliferation through the ERK and AKT/ mTOR pathways. Furthermore, GDNPs facilitated skin wound healing and decreased inflammation in a mouse skin wound model. Conclusion: GDNPs can promote skin wound healing through the ERK and AKT/mTOR pathways. GDNPs thus represent an alternative treatment for chronic skin wounds.

• Genomics & Informatics
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• v.21 no.2
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• pp.22.1-22.15
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• 2023

Kidney renal clear cell carcinoma (KIRC) is one of the most aggressive cancer type of the urinary system. Metastatic KIRC patients have poor prognosis and limited therapeutic options. Ankyrin 3 (ANK3) is a scaffold protein that plays important roles in maintaining physiological function of the kidney and its alteration is implicated in many cancers. In this study, we investigated differential expression of ANK3 in KIRC using GEPIA2, UALCAN, and HPA databases. Survival analysis was performed by GEPIA2, Kaplan-Meier plotter, and OS-kirc databases. Genetic alterations of ANK3 in KIRC were assessed using cBioPortal database. Interaction network and functional enrichment analyses of ANK3-correlated genes in KIRC were performed using GeneMANIA and Shiny GO, respectively. Finally, the TIMER2.0 database was used to assess correlation between ANK3 expression and immune infiltration in KIRC. We found that ANK3 expression was significantly decreased in KIRC compared to normal tissues. The KIRC patients with low ANK3 expression had poorer survival outcomes than those with high ANK3 expression. ANK3 mutations were found in 2.4% of KIRC patients and were frequently co-mutated with several genes with a prognostic significance. ANK3-correlated genes were significantly enriched in various biological processes, mainly involved in peroxisome proliferator-activated receptor (PPAR) signaling pathway, in which positive correlations of ANK3 with PPARA and PPARG expressions were confirmed. Expression of ANK3 in KIRC was significantly correlated with infiltration level of B cell, CD8+ T cell, macrophage, and neutrophil. These findings suggested that ANK3 could serve as a prognostic biomarker and promising therapeutic target for KIRC.

• 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.