• Animal Bioscience
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• v.36 no.11
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• pp.1632-1646
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• 2023

Objective: The objective of the present study was to investigate the effect of dietary betaine (BT) supplementation on the hepatic transcriptome profiles in broiler chickens raised under heat stress (HS) conditions. Methods: A total of 180 (21-d-old) Ross 308 male broiler chicks were allotted to 1 of 3 treatment groups with 6 replicated cages in a completely randomized design. One group was kept under thermoneutral conditions at all times and was fed a basal diet (PC). Other 2 groups were exposed to a cyclic heat stress condition. One of the 2 groups under heat stress conditions was fed the basal diet as a negative control (NC), whereas the other group was fed the basal diet supplemented with 0.2% BT. All chickens were provided with diets and water ad libitum for 21 d. Following the experiment, the liver samples were collected for RNA sequencing analysis. Results: Broiler chickens in NC and BT group had decreased (p<0.05) growth performance. In the transcriptome analysis, the number of differentially expressed genes were identified in the liver by HS conditions and dietary BT supplementation. In the comparison between NC and PC treatments, genes related to energy and nucleic acid metabolism, amino acid metabolism, and immune system were altered by HS, which support the reason why heat-stressed poultry had decreased growth performance. In the comparison between NC and BT treatments, genes related to lipid metabolism, carbohydrate metabolism, and immune system were differently expressed under HS conditions. Conclusion: HS negatively impacts various physiological processes, including DNA replication, metabolism of amino acids, lipids, and carbohydrates, and cell cycle progression in broiler chickens. Dietary BT supplementation, however, offers potential counteractive effects by modulating liver function, facilitating gluconeogenesis, and enhancing immune systems. These findings provide a basis for understanding molecular responses by HS and the possible benefits of dietary BT supplementation in broiler chickens exposed to HS.

• Fisheries and Aquatic Sciences
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• v.6 no.1
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• pp.41-44
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• 2003

Ninety nine random complementary DNA clones from rainbow trout (Oncorhynchus mykiss) liver cDNA library were partially sequenced as one approach to analyze the transcribed sequences of its genome. Of the sequence generated, $64.0\%$ of the ESTs were represented by 29 known genes. Thirty six clones of the unknown gene products potentially represent 31 unique genes. Serum albumin $(16.1\%)$ was the most abundant in the liver. The structural genes in the liver $(19\%)$ were the highly expressed functional category. This research is helpful to understand tissue specific gene expression profile and basic relationship between tissue and functional categories of the genes.

• Journal of Ginseng Research
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• v.44 no.3
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• pp.519-526
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• 2020

Background: Bisphenol A (BPA), known as an endocrine disruptor, is widely used in the world. BPA is reported to cause inflammation-related diseases. Korean Red Ginseng (KRG) has been used safely in human for a long time for the treatment of diverse diseases. KRG has been reported of its mitigating effect on menopausal symptoms and suppress adipose inflammation. Here, we investigate the protective effect of orally administered KRG on the impacts of BPA in the liver and uterus of menopausal mice model. Methods: The transcriptome analysis for the effects of BPA on mice liver was evaluated by Gene Expression Omnibus (GEO) database-based data (GSE26728). In vivo assay to evaluate the protective effect of KRG on BPA impact in ovariectomized (OVX) mice were designed and analyzed by RNA sequencing. Results: We first demonstrated that BPA induced 12 kinds of gene set in the liver of normal mice. The administration of BPA and KRG did not change body, liver, and uterine weight in OVX mice. KRG downregulated BPA-induced inflammatory response and chemotaxis-related gene expression. Several gene set enrichment analysis (GSEA)-derived inflammatory response genes increased by BPA were inhibited by KRG in OVX mice. Conclusion: Our data suggest that BPA has commonly influenced inflammatory response effects on both normal and OVX mice. KRG protects against BPA impact of inflammatory response and chemotaxis in OVX mouse models. Our comparative analysis will provide new insight into the efficacy of KRG on endocrine disrupting chemicals and OVX mouse.

• Animal Bioscience
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• v.37 no.8
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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.

• BMB Reports
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• v.53 no.6
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• pp.299-310
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• 2020

Chronic liver disease progresses through several stages, fatty liver, steatohepatitis, cirrhosis, and eventually, it leads to hepatocellular carcinoma (HCC) over a long period of time. Since a large proportion of patients with HCC are accompanied by cirrhosis, it is considered to be an important factor in the diagnosis of liver cancer. This is because cirrhosis leads to an irreversible harmful effect, but the early stages of chronic liver disease could be reversed to a healthy state. Therefore, the discovery of biomarkers that could identify the early stages of chronic liver disease is important to prevent serious liver damage. Biomarker discovery at liver cancer and cirrhosis has enhanced the development of sequencing technology. Next generation sequencing (NGS) is one of the representative technical innovations in the biological field in the recent decades and it is the most important thing to design for research on what type of sequencing methods are suitable and how to handle the analysis steps for data integration. In this review, we comprehensively summarized NGS techniques for identifying genome, transcriptome, DNA methylome and 3D/4D chromatin structure, and introduced framework of processing data set and integrating multi-omics data for uncovering biomarkers.

• Journal of Veterinary Science
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• v.22 no.3
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• pp.34.1-34.7
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• 2021

Anti-lipopolysaccharide (LPS) antibody administration has the potential benefits of neutralizing and consequently controlling rumen-derived LPS during subacute ruminal acidosis. Four Holstein bulls were used in this crossover study with a 2-week wash-out period. Anti-LPS antibody (0 or 4 g) was administered once daily for 14 days. Significantly lower ruminal LPS and higher 1-h mean ruminal pH were identified in the 4 g group. However, blood metabolites, acute-phase proteins, cytokines, and hepatic transcriptomes were not different between the two groups. Therefore, anti-LPS antibody administration mitigated ruminal LPS release and pH depression without accompanying responses in acute-phase inflammation or hepatic transcriptomic expression.

• Parasites, Hosts and Diseases
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• v.58 no.5
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• pp.513-525
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• 2020

Clonorchis sinensis is a food-borne trematode that infects more than 15 million people. The liver fluke causes clonorchiasis and chronical cholangitis, and promotes cholangiocarcinoma. The underlying molecular pathogenesis occurring in the bile duct by the infection is little known. In this study, transcriptome profile in the bile ducts infected with C. sinensis were analyzed using microarray methods. Differentially expressed genes (DEGs) were 1,563 and 1,457 at 2 and 4 weeks after infection. Majority of the DEGs were temporally dysregulated at 2 weeks, but 519 DEGs showed monotonically changing expression patterns that formed seven distinct expression profiles. Protein-protein interaction (PPI) analysis of the DEG products revealed 5 sub-networks and 10 key hub proteins while weighted co-expression network analysis (WGCNA)-derived gene-gene interaction exhibited 16 co-expression modules and 13 key hub genes. The DEGs were significantly enriched in 16 Kyoto Encyclopedia of Genes and Genomes pathways, which were related to original systems, cellular process, environmental information processing, and human diseases. This study uncovered a global picture of gene expression profiles in the bile ducts infected with C. sinensis, and provided a set of potent predictive biomarkers for early diagnosis of clonorchiasis.

• Development and Reproduction
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• v.24 no.2
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• pp.89-100
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• 2020

Clerodendrum trichotomum is a folk medicine exhibiting anti-hypertension, anti-arthritis, and anti-rheumatism properties. However, little is known about whether the material might prevent hyperuricemia and associated inflammation. In this study, we explored whether C. trichotomum leaf extract (CTE) prevented hyperuricemia induced by potassium oxonate (PO) in mice. CTE (400 mg/kg body weight) significantly reduced the serum uric acid (UA), blood urea nitrogen (BUN), and serum creatinine levels and increased urine UA and creatinine levels. CTE ameliorated PO-induced inflammation and apoptosis by reducing the levels of relevant proteins in kidney tissues. Also, CTE ameliorated both UA-induced inflammatory response in RAW 263.7 cells and UA-induced cytotoxicity in HK-2 cells. In addition, liver transcriptome analysis showed that CTE enriched mainly the genes for mediating positive regulation of MAPK cascade and apoptotic signaling pathways. Together, the results show that CTE effectively prevents hyperuricemia and associated inflammation in PO-induced mice.

• BMB Reports
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• v.51 no.2
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• pp.57-58
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• 2018

An accurate diagnostic marker for detecting early-stage hepatocellular carcinoma (eHCC) is clinically important, since early detection of HCC remarkably improves patient survival. From the integrative analysis of the transcriptome and clinicopathologic data of human multi-stage HCC tissues, we were able to identify barrier-to-autointegration factor 1 (BANF1), procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) and splicing factor 3b subunit 4 (SF3B4) as early HCC biomarkers which could be detected in precancerous lesions of HCC, with superior capabilities to diagnose eHCC compared to the currently popular HCC diagnostic biomarkers: GPC3, GS, and HSP70. We then showed that SF3B4 knockdown caused G1/S cell cycle arrest by recovering $p27^{kip1}$ and simultaneously suppressing cyclins, and CDKs in liver cancer cells. Notably, we demonstrated that aberrant SF3B4 overexpression altered the progress of splicing progress of the tumor suppressor gene, kruppel like factor 4 (KLF4), and resulted in non-functional skipped exon transcripts. This contributes to liver tumorigenesis via transcriptional inactivation of $p27^{kip1}$ and simultaneous activation of Slug genes. Our results suggest that SF3B4 indicates early-stage HCC in precancerous lesions, and also functions as an early-stage driver in the development of liver cancer.

• Journal of Microbiology and Biotechnology
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• v.32 no.2
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• pp.149-159
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• 2022

Cancers of the lung and liver are the top 10 leading causes of cancer death worldwide. Thus, it is essential to identify the genes specifically expressed in these two cancer types to develop new therapeutics. Although many messenger RNA (mRNA) sequencing data related to these cancer cells are available due to the advancement of next-generation sequencing (NGS) technologies, optimized data processing methods need to be developed to identify the novel cancer-specific genes. Here, we conducted an analytical comparison between Bowtie2, a Burrows-Wheeler transform-based alignment tool, and Kallisto, which adopts pseudo alignment based on a transcriptome de Bruijn graph using mRNA sequencing data on normal cells and lung/liver cancer tissues. Before using cancer data, simulated mRNA sequencing reads were generated, and the high Transcripts Per Million (TPM) values were compared. mRNA sequencing reads data on lung/liver cancer cells were also extracted and quantified. While Kallisto could directly give the output in TPM values, Bowtie2 provided the counts. Thus, TPM values were calculated by processing the Sequence Alignment Map (SAM) file in R using package Rsubread and subsequently in python. The analysis of the simulated sequencing data revealed that Kallisto could detect more transcripts and had a higher overlap over Bowtie2. The evaluation of these two data processing methods using the known lung cancer biomarkers concludes that in standard settings without any dedicated quality control, Kallisto is more effective at producing faster and more accurate results than Bowtie2. Such conclusions were also drawn and confirmed with the known biomarkers specific to liver cancer.