• Journal of Ginseng Research
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• 제47권5호
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• pp.645-653
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• 2023

Background: Changes to work-life balance has increased the incidence of cervical cancer among younger people. A minor ginseng saponin known as ginsenoside Rk1 can inhibit the growth and survival of human cancer cells; however, whether ginsenoside Rk1 inhibits HeLa cell proliferation is unknown. Methods and results: Ginsenoside Rk1 blocked HeLa cells in the G0/G1 phase in a dose-dependent manner and inhibited cell division and proliferation. Ginsenoside Rk1 markedly also activated the apoptotic signaling pathway via caspase 3, PARP, and caspase 6. In addition, ginsenoside Rk1 increased LC3B protein expression, indicating the promotion of the autophagy signaling pathway. Protein processing in the endoplasmic reticulum signaling pathway was downregulated in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, consistent with teal-time quantitative PCR and western blotting that showed YOD1, HSPA4L, DNAJC3, and HSP90AA1 expression levels were dramatically decreased in HeLa cells treated with ginsenoside Rk1, with YOD1 was the most significantly inhibited by ginsenoside Rk1 treatment. Conclusion: These findings indicate that the toxicity of ginsenoside Rk1 in HeLa cells can be explained by the inhibition of protein synthesis in the endoplasmic reticulum and enhanced apoptosis, with YOD1 acting as a potential target for cervical cancer treatment.

• Korean Journal of Acupuncture
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• 제41권1호
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• pp.7-15
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• 2024

Objectives : This study aimed to predict the effectiveness and potential of Schizonepeta tenuifolia as an anticancer treatment for non-small cell lung cancer through network-based pharmacology and cellular experiment. Methods : To identify the major bioactive compounds in Schizonepeta tenuifolia, we used the Traditional Chinese Medicine Systems. The target genes for the cancer treatment were selected using the UniProt database and the networked using Cytoscape. We performed functional enrichment analysis based on the Gene Ontology Biological Process and Kyoto Encyclopedia of Genes and Genomes Pathways to predict the mechanisms. To investigate the effect of Schizonepeta tenuifolia on lung cancer cell growth, we treated A549 cells, a lung cancer cell line, with different concentrations of the drug and used the MTT assay for cell viability. Results : Research has shown that the most effective mechanism of active compounds from Schizonepeta tenuifolia is through the pathway of cancer. The results of the network pharmacology analysis indicate that Schizonepeta tenuifolia has potential medicinal value as an adjuvant in anticancer treatment. The concentration-dependent inhibition of cell viability was observed on A549 cells. Furthermore, synergistic anticancer activity with Doxorubicin was also observed. Conclusions : Through a network pharmacological approach, Schizonepeta tenuifolia was predicted to have potential as an anticancer agent, and its efficacy was experimentally demonstrated using A549 cells. These findings suggest that Schizonepeta tenuifolia is a promising candidate for future research.

• 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.

• Animal Bioscience
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• 제37권3호
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• pp.461-470
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• 2024

Objective: The objective of this study was to investigate the genetic diversity, population structure and whole-genome selection signatures of Luxi cattle to reveal its genomic characteristics in terms of meat and carcass traits, skeletal muscle development, body size, and other traits. Methods: To further analyze the genomic characteristics of Luxi cattle, this study sequenced the whole-genome of 16 individuals from the core conservation farm in Shandong region, and collected 174 published genomes of cattle for conjoint analysis. Furthermore, three different statistics (pi, F_st, and XP-EHH) were used to detect potential positive selection signatures related to selection in Luxi cattle. Moreover, gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analyses were performed to reveal the potential biological function of candidate genes harbored in selected regions. Results: The results showed that Luxi cattle had high genomic diversity and low inbreeding levels. Using three complementary methods (pi, F_st, and XP-EHH) to detect the signatures of selection in the Luxi cattle genome, there were 2,941, 2,221 and 1,304 potentially selected genes identified, respectively. Furthermore, there were 45 genes annotated in common overlapping genomic regions covered 0.723 Mb, including PLAG1 zinc finger (PLAG1), dedicator of cytokinesis 3 (DOCK3), ephrin A2 (EFNA2), DAZ associated protein 1 (DAZAP1), Ral GTPase activating protein catalytic subunit alpha 1 (RALGAPA1), mediator complex subunit 13 (MED13), and decaprenyl diphosphate synthase subunit 2 (PDSS2), most of which were enriched in pathways related to muscle growth and differentiation and immunity. Conclusion: In this study, we provided a series of genes associated with important economic traits were found in positive selection regions, and a scientific basis for the scientific conservation and genetic improvement of Luxi cattle.

• 대한한의학회지
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• 제45권1호
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• pp.114-125
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• 2024

Objectives: Network pharmacology is an analysis method that explores drug-centered efficacy and mechanism by constructing a compound-target-disease network based on system biology, and is attracting attention as a methodology for studying herbal medicine that has the characteristics for multi-compound therapeutics. Thus, we investigated the potential functions and pathways of Myrrha on Allergic Rhinitis (AR) via network pharmacology analysis and molecular docking. Methods: Using public databases and PubChem database, compounds of Myrrha and their target genes were collected. The putative target genes of Myrrha and known target genes of AR were compared and found the correlation. Then, the network was constructed using STRING database, and functional enrichment analysis was conducted based on the Gene Ontology (GO) Biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways. Binding-Docking stimulation was performed using CB-Dock. Results: The result showed that total 3 compounds and 55 related genes were gathered from Myrrha. 33 genes were interacted with AR gene set, suggesting that the effects of Myrrha are closely related to AR. Target genes of Myrrha are considerably associated with various pathways including 'Fc epsilon RI signaling pathway' and 'JAK-STAT signaling pathway'. As a result of blinding docking, AKT1, which is involved in both mechanisms, had high binding energies for abietic acid and dehydroabietic acid, which are components of Myrrha. Conclusion: Through a network pharmacological method, Myrrha was predicted to have high relevance with AR by regulating AKT1. This study could be used as a basis for studying therapeutic effects of Myrrha on AR.

• Asian-Australasian Journal of Animal Sciences
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• 제29권3호
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• pp.343-351
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• 2016

Although the chemical, physical, and nutritional properties of bovine milk have been extensively studied, only a few studies have attempted to characterize milk-synthesizing genes using RNA-seq data. RNA-seq data was collected from 21 Holstein samples, along with group information about milk production ability; milk yield; and protein, fat, and solid contents. Meta-analysis was employed in order to generally characterize genes related to milk production. In addition, we attempted to investigate the relationship between milk related traits, parity, and lactation period. We observed that milk fat is highly correlated with lactation period; this result indicates that this effect should be considered in the model in order to accurately detect milk production related genes. By employing our developed model, 271 genes were significantly (false discovery rate [FDR] adjusted p-value<0.1) detected as milk production related differentially expressed genes. Of these genes, five (albumin, nitric oxide synthase 3, RNA-binding region (RNP1, RRM) containing 3, secreted and transmembrane 1, and serine palmitoyltransferase, small subunit B) were technically validated using quantitative real-time polymerase chain reaction (qRT-PCR) in order to check the accuracy of RNA-seq analysis. Finally, 83 gene ontology biological processes including several blood vessel and mammary gland development related terms, were significantly detected using DAVID gene-set enrichment analysis. From these results, we observed that detected milk production related genes are highly enriched in the circulation system process and mammary gland related biological functions. In addition, we observed that detected genes including caveolin 1, mammary serum amyloid A3.2, lingual antimicrobial peptide, cathelicidin 4 (CATHL4), cathelicidin 6 (CATHL6) have been reported in other species as milk production related gene. For this reason, we concluded that our detected 271 genes would be strong candidates for determining milk production.

• Journal of Acupuncture Research
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• 제37권2호
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• pp.128-135
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• 2020

Background: Classical acupuncture is being used in the treatment of rheumatoid arthritis (RA). To explore the biological response to acupuncture, a network-based analysis was performed on gene expression data collected from an animal model of RA treated with acupuncture. Methods: Gene expression data were obtained from published microarray studies on blood samples from rats with collagen induced arthritis (CIA) and non-CIA rats, both treated with manual acupuncture. The weighted gene co-expression network analysis was performed to identify gene clusters expressed in association with acupuncture treatment time and RA status. Gene ontology and pathway analyses were applied for functional annotation and network visualization. Results: A cluster of 347 genes were identified that differentially downregulated expression in association with acupuncture treatment over time; specifically in rats with CIA with module-RA correlation at 1 hour after acupuncture (-0.27; p < 0.001) and at 34 days after acupuncture (-0.33; p < 0.001). Functional annotation showed highly significant enrichment of porphyrin-containing compound biosynthetic processes (p < 0.001). The network-based analysis also identified a module of 140 genes differentially expressed between CIA and non-CIA in rats (p < 0.001). This cluster of genes was enriched for antigen processing and presentation of exogenous peptide antigen (p < 0.001). Other functional gene clusters previously reported in earlier studies were also observed. Conclusion: The identified gene expression networks and their hub-genes could help with the understanding of mechanisms involved in the pathogenesis of RA, as well understanding the effects of acupuncture treatment of RA.

• Journal of Animal Science and Technology
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• 제63권4호
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• pp.934-953
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• 2021

Ciglitazone is a member of the thiazolidinedione family, and specifically binds to peroxisome proliferator-activated receptor-γ (PPARγ), thereby promoting adipocyte differentiation. We hypothesized that ciglitazone as a PPARγ ligand in the absence of an adipocyte differentiation cocktail would increase adiponectin and adipogenic gene expression in bovine satellite cells (BSC). Muscle-derived BSCs were isolated from six, 18-month-old Yanbian Yellow Cattle. The BSC were cultured for 96 h in differentiation medium containing 5 µM ciglitazone (CL), 10 µM ciglitazone (CM), or 20 µM ciglitazone (CH). Control (CON) BSC were cultured only in a differentiation medium (containing 2% horse serum). The presence of myogenin, desmin, and paired box 7 (Pax7) proteins was confirmed in the BSC by immunofluorescence staining. The CL, CM, and CH treatments produced higher concentrations of triacylglycerol and lipid droplet accumulation in myotubes than those of the CON treatment. Ciglitazone treatments significantly increased the relative expression of PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα), C/EBPβ, fatty acid synthase, stearoyl-CoA desaturase, and perilipin 2. Ciglitazone treatments increased gene expression of Pax3 and Pax7 and decreased expression of myogenic differentiation-1, myogenin, myogenic regulatory factor-5, and myogenin-4 (p < 0.01). Adiponectin concentration caused by ciglitazone treatments was significantly greater than CON (p < 0.01). RNA sequencing showed that 281 differentially expressed genes (DEGs) were found in the treatments of ciglitazone. DEGs gene ontology (GO) analysis showed that the top 10 GO enrichment significantly changed the biological processes such as protein trimerization, negative regulation of cell proliferation, adipocytes differentiation, and cellular response to external stimulus. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that DEGs were involved in the p53 signaling pathway, PPAR signaling pathway, biosynthesis of amino acids, tumor necrosis factor signaling pathway, non-alcoholic fatty liver disease, PI3K-Akt signaling pathway, and Wnt signaling pathway. These results indicate that ciglitazone acts as PPARγ agonist, effectively increases the adiponectin concentration and adipogenic gene expression, and stimulates the conversion of BSC to adipocyte-like cells in the absence of adipocyte differentiation cocktail.

• Asian-Australasian Journal of Animal Sciences
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• 제32권9호
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• pp.1458-1468
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• 2019

Objective: As one of the most important metabolic organs, the liver plays vital roles in modulating the lipid metabolism. This study was to compare miRNA expression profiles of the Large White liver between two different developmental periods and to identify candidate miRNAs for lipid metabolism. Methods: Eight liver samples were collected from White Large of 70-day fetus (P70) and of 70-day piglets (D70) (with 4 biological repeats at each development period) to construct sRNA libraries. Then the eight prepared sRNA libraries were sequenced using Illumina next-generation sequencing technology on HiSeq 2500 platform. Results: As a result, we obtained 346 known and 187 novel miRNAs. Compared with the D70, 55 down- and 61 up-regulated miRNAs were shown to be significantly differentially expressed (DE). Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis indicated that these DE miRNAs were mainly involved in growth, development and diverse metabolic processes. They were predicted to regulate lipid metabolism through adipocytokine signaling pathway, mitogen-activated protein kinase, AMP-activated protein kinase, cyclic adenosine monophosphate, phosphatidylinositol 3 kinase/protein kinase B, and Notch signaling pathway. The four most abundantly expressed miRNAs were miR-122, miR-26a and miR-30a-5p (miR-122 only in P70), which play important roles in lipid metabolism. Integration analysis (details of mRNAs sequencing data were shown in another unpublished paper) revealed that many target genes of the DE miRNAs (miR-181b, miR-145-5p, miR-199a-5p, and miR-98) might be critical regulators in lipid metabolic process, including acyl-CoA synthetase long chain family member 4, ATP-binding casette A4, and stearyl-CoA desaturase. Thus, these miRNAs were the promising candidates for lipid metabolism. Conclusion: Our study provides the main differences in the Large White at miRNA level between two different developmental stages. It supplies a valuable database for the further function and mechanism elucidation of miRNAs in porcine liver development and lipid metabolism.

• Asian-Australasian Journal of Animal Sciences
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• 제32권3호
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• pp.320-333
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• 2019

Objective: The Shanghai Holstein cattle breed is susceptible to severe mastitis and other diseases due to the hot weather and long-term humidity in Shanghai, which is the main distribution centre for providing Holstein semen to various farms throughout China. Our objective was to determine the genetic mechanisms influencing economically important traits, especially diseases that have huge impact on the yield and quality of milk as well as reproduction. Methods: In our study, we detected the structural variations of 1,092 Shanghai Holstein cows by using next-generation sequencing. We used the DELLY software to identify deletions and insertions, cn.MOPS to identify copy-number variants (CNVs). Furthermore, we annotated these structural variations using different bioinformatics tools, such as gene ontology, cattle quantitative trait locus (QTL) database and ingenuity pathway analysis (IPA). Results: The average number of high-quality reads was 3,046,279. After filtering, a total of 16,831 deletions, 12,735 insertions and 490 CNVs were identified. The annotation results showed that these mapped genes were significantly enriched for specific biological functions, such as disease and reproduction. In addition, the enrichment results based on the cattle QTL database showed that the number of variants related to milk and reproduction was higher than the number of variants related to other traits. IPA core analysis found that the structural variations were related to reproduction, lipid metabolism, and inflammation. According to the functional analysis, structural variations were important factors affecting the variation of different traits in Shanghai Holstein cattle. Our results provide meaningful information about structural variations, which may be useful in future assessments of the associations between variations and important phenotypes in Shanghai Holstein cattle. Conclusion: Structural variations identified in this study were extremely different from those of previous studies. Many structural variations were found to be associated with mastitis and reproductive system diseases; these results are in accordance with the characteristics of the environment that Shanghai Holstein cattle experience.