The interaction of the genes involved in intestinal development is the molecular basis of the regulatory mechanisms of intestinal development. The objective of this study was to identify the significant pathways and key genes that regulate intestinal development in Landrace piglets, and elucidate their rules of operation. The differential expression of genes related to intestinal development during suckling time was investigated using a porcine genome array. Time sequence profiles were analyzed for the differentially expressed genes to obtain significant expression profiles. Subsequently, the most significant profiles were assayed using Gene Ontology categories, pathway analysis, network analysis, and analysis of gene co-expression to unveil the main biological processes, the significant pathways, and the effective genes, respectively. In addition, quantitative real-time PCR was carried out to verify the reliability of the results of the analysis of the array. The results showed that more than 8000 differential expression transcripts were identified using microarray technology. Among the 30 significant obtained model profiles, profiles 66 and 13 were the most significant. Analysis of profiles 66 and 13 indicated that they were mainly involved in immunity, metabolism, and cell division or proliferation. Among the most effective genes in these two profiles, CN161469, which is similar to methylcrotonoyl-Coenzyme A carboxylase 2 (beta), and U89949.1, which encodes a folate binding protein, had a crucial influence on the co-expression network.
Choudhary, Shanti;Li, Wenli;Bickhart, Derek;Verma, Ramneek;Sethi, R.S.;Mukhopadhyay, C.S.;Choudhary, Ratan K.
Journal of Animal Science and Technology
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제60권7호
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pp.18.1-18.12
/
2018
Background: Xanthosine treatment has been previously reported to increase mammary stem cell population and milk production in cattle and goats. However, the underlying molecular mechanisms associated with the increase in stem cell population and milk production remain unclear. Methods: Primiparous Beetal goats were assigned to the study. Five days post-partum, one mammary gland of each goat was infused with xanthosine (TRT) twice daily ($2{\times}$) for 3 days consecutively, and the other gland served as a control (CON). Milk samples from the TRT and CON glands were collected on the 10th day after the last xanthosine infusion and the total RNA was isolated from milk fat globules (MEGs). Total RNA in MFGs was mainly derived from the milk epithelial cells (MECs) as evidenced by expression of milk synthesis genes. Significant differentially expressed genes (DEGs) were subjected to Gene Ontology (GO) terms using PANTHER and gene networks were generated using STRING db. Results: Preliminary analysis indicated that each individual goat responded to xanthosine treatment differently, with this trend being correlated with specific DEGs within the same animal's mammary gland. Several pathways are impacted by these DEGs, including cell communication, cell proliferation and anti-microbials. Conclusions: This study provides valuable insights into transcriptomic changes in milk producing epithelial cells in response to xanthosine treatment. Further characterization of DEGs identified in this study is likely to delineate the molecular mechanisms of increased milk production and stem or progenitor cell population by the xanthosine treatment.
KUGI (Korean UniGene Information) database contains the annotation information of the cDNA sequences obtained from the disease samples prevalent in Korean. A total of about 157,000 5'-EST high throughput sequences collected from cDNA libraries of stomach, liver, and some cancer tissues or established cell lines from Korean patients were clustered to about 35,000 contigs. From each cluster a representative clone having the longest high quality sequence or the start codon was selected. We stored the sequences of the representative clones and the clustered contigs in the KUGI database together with their information analyzed by running Blast against RefSeq, human mRNA, and UniGene databases from NCBI. We provide a web-based search engine fur the KUGI database using two types of user interfaces: attribute-based search and similarity search of the sequences. For attribute-based search, we use DBMS technology while we use BLAST that supports various similarity search options. The search system allows not only multiple queries, but also various query types. The results are as follows: 1) information of clones and libraries, 2) accession keys, location on genome, gene ontology, and pathways to public databases, 3) links to external programs, and 4) sequence information of contig and 5'-end of clones. We believe that the KUGI database and search system may provide very useful information that can be used in the study for elucidating the causes of the disease that are prevalent in Korean.
Flammulina velutipes is a popular edible basidiomycete mushroom found in East Asia and is commonly known as winter mushroom. Mushroom development showing dramatic morphological changes by different environmental factors is scientifically and commercially interesting. To create a genetic database and isolate genes regulated during mushroom development, cDNA libraries were constructed from three developmental stages of mycelium, primordium, and fruit body in F. velutipes. We generated a total of 5,431 expressed sequence tags (ESTs) from randomly selected clones from the three cDNA libraries. Of these, 3,332 different unique genes (unigenes) were consistent with 2,442 (73%) singlets and 890 (27%) contigs. This corresponds to a redundancy of 39%. Using a homology search in the gene ontology database, the EST unigenes were classified into the three categories of molecular function (28%), biological process (29%), and cellular component (6%). Comparative analysis found great variations in the unigene expression pattern among the three different unigene sets generated from the cDNA libraries of mycelium, primordium, and fruit body. The 19-34% of total unigenes were unique to each unigene set and only 3% were shared among all three unigene sets. The unique and common representation in F. velutipes unigenes from the three different cDNA libraries suggests great differential gene expression profiles during the different developmental stages of F. velutipes mushroom.
Several human diseases have been associated with mitochondrial voltage-dependent anion channel-1 (VDAC1) due to its role in calcium ion transportation and apoptosis. Recent studies suggest that VDAC1 may interact with endothelium-dependent nitric oxide synthase (eNOS). Decreased VDAC1 expression may limit the physical interaction between VDAC1 and eNOS and thus impair nitric oxide production, leading to cardiovascular diseases, including pulmonary arterial hypertension (PAH). In this report, we conducted meta-analysis of genome-wide expression data to identify VDAC1 influenced genes implicated in PAH pathobiology. First, we identified the genes differentially expressed between wild-type and Vdac1 knockout mouse embryonic fibroblasts in hypoxic conditions. These genes were deemed to be influenced by VDAC1 deficiency. Gene ontology analysis indicates that the VDAC1 influenced genes are significantly associated with PAH pathobiology. Second, a molecular signature derived from the VDAC1 influenced genes was developed. We suggest that, VDAC1 has a protective role in PAH and the gene expression signature of VDAC1 influenced genes can be used to i) predict severity of pulmonary hypertension secondary to pulmonary diseases, ii) differentiate idiopathic pulmonary artery hypertension (IPAH) patients from controls, and iii) differentiate IPAH from connective tissue disease associated PAH.
Background: Lapatinib, a dual tyrosine kinase inhibitor that interrupts the epidermal growth factor receptor (EGFR) and HER2/neu pathways, has been indicated to have significant efficacy in treating HER2-positive breast cancer. However, acquired drug resistance has become a very serious clinical problem that hampers the use of this agent. In this study, we aimed to screen small molecule drugs that might reverse lapatinib-resistance of breast cancer by exploring differentially expressed genes (DEGs) via a bioinformatics method. Materials and Methods: We downloaded the gene expression profile of BT474-J4 (acquired lapatinib-resistant) and BT474 (lapatinib-sensitive) cell lines from the Gene Expression Omnibus (GEO) database and selected differentially expressed genes (DEGs) using dChip software. Then, gene ontology and pathway enrichment analyses were performed with the DAVID database. Finally, a connectivity map was utilized for predicting potential chemicals that reverse lapatinib-resistance. Results: A total of 1, 657 DEGs were obtained. These DEGs were enriched in 10 pathways, including cell cycling, regulation of actin cytoskeleton and focal adhesion associate examples. In addition, several small molecules were screened as the potential therapeutic agents capable of overcoming lapatinib-resistance. Conclusions: The results of our analysis provided a novel strategy for investigating the mechanism of lapatinib-resistance and identifying potential small molecule drugs for breast cancer treatment.
Purpose: Prostate cancer caused by the abnormal disorderly growth of prostatic acinar cells is the most prevalent cancer of men in western countries. We aimed to screen out differentially expressed genes (DEGs) and explore small molecule drugs for prostate cancer. Materials and Methods: The GSE3824 gene expression profile of prostate cancer was downloaded from Gene Expression Omnibus database which including 21 normal samples and 18 prostate cancer cells. The DEGs were identified by Limma package in R language and gene ontology and pathway enrichment analyses were performed. In addition, potential regulatory microRNAs and the target sites of the transcription factors were screened out based on the molecular signature database. In addition, the DEGs were mapped to the connectivity map database to identify potential small molecule drugs. Results: A total of 6,588 genes were filtered as DEGs between normal and prostate cancer samples. Examples such as ITGB6, ITGB3, ITGAV and ITGA2 may induce prostate cancer through actions on the focal adhesion pathway. Furthermore, the transcription factor, SP1, and its target genes ARHGAP26 and USF1 were identified. The most significant microRNA, MIR-506, was screened and found to regulate genes including ITGB1 and ITGB3. Additionally, small molecules MS-275, 8-azaguanine and pyrvinium were discovered to have the potential to repair the disordered metabolic pathways, abd furthermore to remedy prostate cancer. Conclusions: The results of our analysis bear on the mechanism of prostate cancer and allow screening for small molecular drugs for this cancer. The findings have the potential for future use in the clinic for treatment of prostate cancer.
Skin is a major thermoregulatory organ in the body controlling homeothermy, a critical function for climate adaptation. We compared genes expressed between tropical- and temperate-adapted cattle to better understand genes involved in climate adaptation and hence thermoregulation. We profiled the skin of representative tropical and temperate cattle using RNA-seq. A total of 214,754,759 reads were generated and assembled into 72,993,478 reads and were mapped to unique regions in the bovine genome. Gene coverage of unique regions of the reference genome showed that of 24,616 genes, only 13,130 genes (53.34%) displayed more than one count per million reads for at least two libraries and were considered suitable for downstream analyses. Our results revealed that of 255 genes expressed differentially, 98 genes were upregulated in tropically-adapted White Fulani (WF; Bos indicus) and 157 genes were down regulated in WF compared to Angus, AG (Bos taurus). Fifteen pathways were identified from the differential gene sets through gene ontology and pathway analyses. These include the significantly enriched melanin metabolic process, proteinaceous extracellular matrix, inflammatory response, defense response, calcium ion binding and response to wounding. Quantitative PCR was used to validate six representative genes which are associated with skin thermoregulation and epithelia dysfunction (mean correlation 0.92; p < 0.001). Our results contribute to identifying genes and understanding molecular mechanisms of skin thermoregulation that may influence strategic genomic selection in cattle to withstand climate adaptation, microbial invasion and mechanical damage.
Background: Panax ginseng has been used in traditional medicine to strengthen the body and mental well-being of humans for thousands of years. Many elite ginseng cultivars have been developed, and ginseng cultivation has become well established during the last century. However, heat stress poses an important threat to the growth and sustainable production of ginseng. Efforts have been made to study the effects of high temperature on ginseng physiology, but knowledge of the molecular responses to heat stress is still limited. Methods: We sequenced the transcriptomes (RNA-Seq) of two ginseng cultivars, Chunpoong (CP) and Yunpoong (YP), which are sensitive and resistant to heat stress, respectively, after 1- and 3-week heat treatments. Differential gene expression and gene ontology enrichment along with profiled chlorophyll contents were performed. Results: CP is more sensitive to heat stress than YP and exhibited a lower chlorophyll content than YP. Moreover, heat stress reduced the chlorophyll content more rapidly in CP than in YP. A total of 329 heat-responsive genes were identified. Intriguingly, genes encoding chlorophyll a/b-binding proteins, WRKY transcription factors, and fatty acid desaturase were predominantly responsive during heat stress and appeared to regulate photosynthesis. In addition, a genome-wide scan of photosynthetic and sugar metabolic genes revealed reduced transcription levels for ribulose 1,5-bisphosphate carboxylase/oxygenase under heat stress, especially in CP, possibly attributable to elevated levels of soluble sugars. Conclusion: Our comprehensive genomic analysis reveals candidate loci/gene targets for breeding and functional studies related to developing high temperature-tolerant ginseng varieties.
Objectives : Because predicting the potential efficacy and mechanisms of Korean medicines is challenging due to their high complexity, employing an approach based on network pharmacology could be effective. In this study, network pharmacological analysis was utilized to anticipate the effects of YunPye-Hwan (YPH) in treating Chronic obstructive pulmonary disease (COPD). Methods : Compounds and their related target genes of YPH were gathered from the TCMSP and PubChem databases. These target genes of YPH were subsequently compared with gene sets associated with COPD to assess correlation. Next, core genes were identified through a two-step screening process, and finally, functional enrichment analysis of these core genes was conducted using both Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways. Results : A total of 15 compounds and 437 target genes were gathered, resulting in a network comprising 473 nodes and 14,137 edges. Among them, 276 genes overlapped with gene sets associated with COPD, indicating a significant correlation between YPH and COPD. Functional enrichment analysis of the 18 core genes revealed biological processes and pathways such as "miRNA Transcription," "Nucleic Acid-Templated Transcription," "DNA-binding Transcription Factor Activity," "MAPK signaling pathway," and "TNF signaling pathway" were implicated. Conclusion : YPH exhibited significant relevance to COPD by modulating cell proliferation, differentiation, inflammation, and cell death pathways. This study could serve as a foundational framework for further research investigating the potential use of YPH in the treatment of COPD.
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