• Molecules and Cells
• /
• v.37 no.7
• /
• pp.547-553
• /
• 2014

Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and $TGF{\beta}$ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.

• Journal of Life Science
• /
• v.29 no.7
• /
• pp.809-816
• /
• 2019

The ubiquitous plant metabolite p-coumaric acid (p-CA) has antioxidant and anti-inflammatory properties, but its anti-cancer activity has not been established in gastric cancer cell lines. In this study, we investigated the effects of p-CA on the proliferation and transcriptome profile of SNU16 gastric cancer cells. Treatment with p-CA induced apoptosis of the SNU-16 cells by regulating the expression of pro-apoptotic and anti-apoptotic proteins, such as Bcl-2, poly (ADP-ribose) polymerase (PARP), Bax, procaspase-3, and cleaved-caspase-3. The genes differentially expressed in response to p-CA treatment of the SNU-16 cells were identified by RNA sequencing analysis. Genes regulated by p-CA were involved mainly in the inflammatory response, apoptotic processes, cell cycle, and immune response. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the phosphatidylinositol-3-kinase-Akt and cancer signaling pathways were altered by p-CA. Protein-protein interaction (PPI) network analysis also revealed that p-CA treatment was correlated with differential expression of genes associated with the inflammatory response and cancer. Collectively, these results suggest that p-CA has potential utility in gastric cancer prevention.

• Animal Bioscience
• /
• v.37 no.1
• /
• pp.28-38
• /
• 2024

Objective: Tibetan chickens, which have unique adaptations to extreme high-altitude environments, exhibit phenotypic and physiological characteristics that are distinct from those of lowland chickens. However, the mechanisms underlying hypoxic adaptation in the liver of chickens remain unknown. Methods: RNA-sequencing (RNA-Seq) technology was used to assess the differentially expressed genes (DEGs) involved in hypoxia adaptation in highland chickens (native Tibetan chicken [HT]) and lowland chickens (Langshan chicken [LS], Beijing You chicken [BJ], Qingyuan Partridge chicken [QY], and Chahua chicken [CH]). Results: A total of 352 co-DEGs were specifically screened between HT and four native lowland chicken breeds. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses indicated that these co-DEGs were widely involved in lipid metabolism processes, such as the peroxisome proliferator-activated receptors (PPAR) signaling pathway, fatty acid degradation, fatty acid metabolism and fatty acid biosynthesis. To further determine the relationship from the 352 co-DEGs, protein-protein interaction network was carried out and identified eight genes (ACSL1, CPT1A, ACOX1, PPARC1A, SCD, ACSBG2, ACACA, and FASN) as the potential regulating genes that are responsible for the altitude difference between the HT and other four lowland chicken breeds. Conclusion: This study provides novel insights into the molecular mechanisms regulating hypoxia adaptation via lipid metabolism in Tibetan chickens and other highland animals.

• Genomics & Informatics
• /
• v.20 no.3
• /
• pp.27.1-27.13
• /
• 2022

Oral squamous cell carcinoma (OSCC) is the most prevalent head and neck malignancy, with frequent cervical lymph-node metastasis, leading to a poor prognosis in OSCC patients. The present study aimed to identify potential markers, including microRNAs (miRNAs) and genes, significantly involved in the etiology of early-stage OSCC. Additionally, the main OSCC's dysregulated Gene Ontology annotations and significant signaling pathways were identified. The dataset GSE45238 underwent multivariate statistical analysis in order to distinguish primary OSCC tissues from healthy oral epithelium. Differentially expressed miRNAs (DEMs) with the criteria of p-value < 0.001 and |Log2 fold change| > 1.585 were identified in the two groups, and subsequently, validated targets of DEMs were identified. A protein interaction map was constructed, hub genes were identified, significant modules within the network were illustrated, and significant pathways and biological processes associated with the clusters were demonstrated. Using the GEPI2 database, the hub genes' predictive function was assessed. Compared to the healthy controls, main OSCC had a total of 23 DEMs. In patients with head and neck squamous cell carcinoma (HNSCC), upregulation of CALM1, CYCS, THBS1, MYC, GATA6, and SPRED3 was strongly associated with a poor prognosis. In HNSCC patients, overexpression of PIK3R3, GIGYF1, and BCL2L11 was substantially correlated with a good prognosis. Besides, "proteoglycans in cancer" was the most significant pathway enriched in the primary OSCC. The present study results revealed more possible mechanisms mediating primary OSCC and may be useful in the prognosis of the patients with early-stage OSCC.

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

• Genomics & Informatics
• /
• v.21 no.4
• /
• pp.46.1-46.10
• /
• 2023

Colon adenocarcinoma (COAD) is the predominant type of colorectal cancer. Early diagnosis and treatment can significantly improve the prognosis of COAD patients. Anoctamin 7 (ANO7), an anion channel protein, has been implicated in prostate cancer and other types of cancer. In this study, we analyzed the expression of ANO7 and its correlation with clinicopathological characteristics among COAD patients using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and the University of Alabama at Birmingham CANcer (UALCAN) databases. The GEPIA2, Kaplan-Meier plotter, and the Survival Genie platform were employed for survival analysis. The co-expression network and potential function of ANO7 in COAD were analyzed using GeneFriends, the Database for Annotation, Visualization and Integrated Discovery (DAVID), GeneMANIA, and Pathway Studio. Our data analysis revealed a significant reduction in ANO7 expression levels within COAD tissues compared to normal tissues. Additionally, ANO7 expression was found to be associated with race and histological subtype. The COAD patients exhibiting low ANO7 expression had lower survival rates compared to those with high ANO7 expression. The genes correlated with ANO7 were significantly enriched in proteolysis and mucin type O-glycan biosynthesis pathway. Furthermore, ANO7 demonstrated a direct interaction and a positive co-expression correlation with mucin 2 (MUC2). In conclusion, our findings suggest that ANO7 might serve as a potential prognostic biomarker and potentially plays a role in proteolysis and mucin biosynthesis in the context of COAD.

• IMMUNE NETWORK
• /
• v.2 no.3
• /
• pp.142-149
• /
• 2002

Background: Our previous study showed that purified protein derivative (PPD)-stimulated pleural mononuclear cells (PMC) from tuberculous pleurisy (Tbp) produced significantly more $IFN-{\gamma}$ (10- to 70-fold) after in vitro PPD stimulation than freshly isolated pleural cells from malignant pleurisy. The present study was designed to determine whether blocking the CD40-CD40 ligand (CD40L) interaction decreases $IFN-{\gamma}$ production by altering IL-12 levels. Methods: IL-12 and $IFN-{\gamma}$ production after neutralizing anti-CD40L antibody treatment was compared to the efficacy of anti-CD80, anti-CD86, and a combination of anti-CD80 and CD86 (CD80+86) monoclonal antibodies (mAb). These activities were measured by enzyme-linked immunosorbent assays (ELISAs) and reverse transcription-polymerase chain reaction (RT-PCR), after in vitro stimulation with PPO antigen (Ag). Results: Neutralization of CD80, CD86 and CD80+86 did not decrease $IFN-{\gamma}$ and IL-12 production in Tbp-PMC, whereas neutralization of CD40L significantly depressed IL-12 p40 and $IFN-{\gamma}$. In addition, neutralization of CD40L completely inhibited IL-12 p40 and $IFN-{\gamma}$ mRNA expression. Conclusion: The CD40-CD40L interaction might play a major role in IL-12 and $IFN-{\gamma}$ production in Tbp-PMC, thus contributing to protective immunity in human tuberculosis.

• Proceedings of the Korea Society for Industrial Systems Conference
• /
• 2002.11a
• /
• pp.3-13
• /
• 2002

고석하 등(2002)은 인터넷 소매상이 상품 품목의 명목 가격과 배송료를 이용해서 고객의 일회 총 구매 비용을 조절한다는 것을 밝혔다. 고석하 등(2002)은 같은 내용의 상품 조합을 인터넷 시장에서 구매하기 위한 비용과 전통 시장에서 구매하기 위한 비용을 비교하였다. 분석 결과, 그 교호작용과 함께, 상품 종류와 일회 구매액/가격의 크기의 두 요소가 인터넷 시장의 전통 시장에 대한 총 구매비용 할인율의 변동의 약 60%내지 80%를 설명할 수 있다는 것을 보여주었다. 한편, 구매액/가격은 인터넷 시장에서의 해당 산포도(전통 시장의 그것에 대비한)에는 거의 영향을 미치지 못하며, 상품의 종류도 산포도에는 할인율에서와 같이 큰 영향을 미치지 않았다. 인터넷 시장의 가격이나 구매비용 산포도는 상품 특성이나 구매액 크기 이외의 다른 요인에 의해서 주로 영향을 받는 것으로 나타났다. 따라서, 본 논문에서는 가격 요인 이외의 경제적 경쟁요인에 관한 실증연구로서, 2002년 6월 17일부터 20일까지, 소프트웨어, PC와 주변기기, 휴대폰, 가전제품, CD, 화장품, 그리고 책의 7가지 산업 전문 쇼핑몰과 종합 쇼핑몰을 대상으로, 인터넷 시장에서 수행되고 있는 경제적인 비 가격 경쟁요인에 관한 실증 조사를 실시하였다. 조사 결과, 인터넷 시장에서 수행되고 있는 경제적인 비 가격 경쟁요인은 매우 다양하며, 상품별로도 다른 특성을 보이고 있는 것으로 밝혀졌다. 인터넷 소매상의 경제적인 비 가격 경쟁요인은 크게 배송료 면제와 배송료 외 인센티브 제도로 구분된다 본 논문에서는 경제적인 비 가격 경쟁요인의 모든 경우의 수를 고려할 수 있도록, 코드표를 작성하여 정리하고 분석하였다.전체 분석정보의 공유가 필수적으로 발생하게 됨으로, 유전체 정보와 임상정보의 통합은 미래 의료환경에 필수기능이 될 것이다. 3) 각 생명공학 연구소에서 사용하는 첨단 분석 장비와 생명공학 정보시스템의 자동 연계가 필요하다. 현재 국내에는 전국적인 초고속정보망이 가동되어 웹을 기반으로 하는 생명정보의 공유는 기술적으로 문제가 될 수 없으나 임상정보의 유전체연구에 그리고 유전체연구정보의 임상활용은 다양한 문제를 내포하고 있다. 이에 영상을 포함한 환자정보의 유전체연구센터와 병원정보시스템과의 효율적인 연계통합 운영을 위해 국내에서는 초기 도입단계에 있는 국제적인 보건의료정보의 표준인 Health Level 7 (textural information 공유), DICOM (image 및 wave 공유), 관련 ISO표준, WHO의 ICD9/10 (질병분류), LOINC (검사 및 관련용어), SNOMED International (의학용어) 등을 활용하여야 한다.matrix. The prediction system gives about 50% of sensitivity and 98% of specificity, Based on the PID matrix, we develop a system providing several interaction information-finding services in the Internet. The system, named PreDIN (Prediction-oriented Database of Interaction Network) provides interacting domain finding services and interacting protein

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2010.05a
• /
• pp.14-14
• /
• 2010

Plastid proteomics are essential organelles present in virtually all cells in plants and green algae. Plastids are responsible for the synthesis and storage of key molecules required for the basic architecture and functions of plant cells. The proteome of plastid, and in particular of chloroplast, have received significant amounts of attention in recent years. Various fractionation and mass spectrometry (MS) techniques have been applied to catalogue the chloroplast proteome and its sub-organelles compartments. To better understanding the function of the lumenal sub-organelles within the thylakoid network, we have carried out a systematical analysis and identification of the lumenal proteins in the thylakoid of wheat by using Tricine-SDS-PAGE, and LTQ-ESI-FTICR mass spectrometry followed by SWISS-PROT database searching. We isolation and fractionation these membrane from fully developed wheat leaves using a combination of differential and gradient centrifugation couple to high speed ultra-centrifuge. After collecting all proteins to eliminate possible same proteins, we estimated that there are 407 different proteins including chloroplast, chloroplast stroma, lumenal, and thylakoid membrane proteins excluding 20 proteins, which were identified in nucleus, cytoplasm and mitochondria. A combination of these three programs (PSORT, TargetP, TMHMM, and TOPPRED) was found to provide a useful tool for evaluating chloroplast localization, transit peptide, transmembranes, and also could reveal possible alternative processing sites and dual targeting. Finally, we report also sub-cellular location specific protein interaction network using Cytoscape software, which provides further insight into the biochemical pathways of photosynthesis. The present work helps understanding photosynthesis process in wheat at the molecular level and provides a new overview of the biochemical machinery of the thylakoid in wheat.

• IMMUNE NETWORK
• /
• v.3 no.1
• /
• pp.1-7
• /
• 2003

Type II collagen (CII), major component of hyaline cartilage, has been considered as an auto-antigen in rheumatoid arthritis (RA). However, the clinical and biological significances with regard to the CII autoimmunity need to be clarified in human RA. The presence of antibodies to CII has been identified in sera, synovial fluid, and cartilage of patients with RA. In our study, the increased titer of IgG anti-CII in sera was well correlated with C-reactive protein, suggesting that this antibody may reflect the inflammatory status of RA. The titer of anti-CII antibodies (anti-CII Abs) tended to be higher in early stages of diseases. In our extending study, among 997 patients with RA, 269 (27.0%) were positive for circulatory IgG antibody to CII, those levels were fluctuated over time. It is hard to assess the significant amount of T cell responses to CII and CII (255~274) in RA. By using a sensitive method of antigen specific mixed lymphocyte culture, we can detect the presence of CII-reactive T cells in peripheral blood mononuclear cells of RA patients. Sixty seven (46.9%) of 143 patients showed positive CII reactive T cell responses to CII or CII (255~274). The frequencies of CII reactive T cells were more prominent in inflamed synovial fluid (SF) than in peripheral blood. These T cells could be clonally expanded after consecutive stimulation of CII with feeding of autologous irradiated antigen presenting cells (APC). Moreover, the production of Th1-related cytokine, such as IFN-${\gamma}$, was strongly up-regulated by CII reactive T cells. These data suggest that T cells responding to CII, which are probably presenting the IFN-${\gamma}$ producing cells, may play an important role in the perpetuation of inflammatory process in RA. To evaluate the effector function of CII reactive T cells, we investigated the effect of CII reactive T cells and fibroblasts-like synoviocytes (FLS) interaction on the production of pro-inflammatory cytokines. When the CII reactive T cells were co-cultured with FLS, the production of IL-15 and TNF-${\alpha}$ from FLS were significantly increased (2 to 3 fold increase) and this increase was clearly presented in accord to the expansion of CII reactive T cells. In addition, the production of IFN-${\gamma}$ and IL-17, T cell derived cytokines, were also increased by the co-incubation of CII reactive T cells with FLS. We also examined the impact of CII reactive T cells on chemokines production. When FLS were co-cultured with CII stimulated T cells, the production of IL-8, MCP-1, and MIP-1${\alpha}$ were significantly enhanced. The increased production of these chemokines was strongly correlated with increase the frequency of CII reactive T cells. Conclusively, immune response to CII was frequently found in RA. Activated T cells in response to CII contributed to increase the production of proinflammatory cytokines and chemokines, which were critical for inflammatory responses in RA. The interaction of CII-reactive T cells with FLS further augmented this phenomenon. Taken together, our recent studies have suggested that autoimmunity to CII could play a crucial role not only in the initiation but amplification/perpetuation of inflammatory process in human RA.