• Genomics & Informatics
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• 제21권2호
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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.

• IMMUNE NETWORK
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• 제10권2호
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• pp.35-45
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• 2010

Background: Expression of recombinant antibodies and their derivatives fused with other functional molecules such as alkaline phosphatase in Escherichia coli is important in the development of molecular diagnostic reagents for biomedical research. Methods: We investigated the possibility of applying a well-known Fos-Jun zipper to dimerize $V_H$ and $V_L$ fragments originated from the Fab clone (SP 112) that recognizes pyruvate dehydrogenase complex-E2 (PDC-E2), and demonstrated that the functional zipFv-112 and its alkaline phosphatase fusion molecules (zipFv-AP) can be produced in the cytoplasm of Origami(DE3) trxB gor mutant E. coli strain. Results: The zipFv-AP fusion molecules exhibited higher antigen-binding signals than the zipFv up to a 10-fold under the same experimental conditions. However, conformation of the zipFv-AP seemed to be influenced by the location of an AP domain at the C-terminus of $V_H$ or $V_L$ domain [zipFv-112(H-AP) or zipFv-112(L-AP)], and inclusion of an AraC DNA binding domain at the C-terminus of VH of the zipFv-112(L-AP), termed zipFv-112(H-AD/L-AP), was also beneficial. Cytoplasmic co-expression of disulfide-binding isomerase C (DsbC) helped proper folding of the zipFv-112(H-AD/L-AP) but not significantly. Conclusion: We believe that our zipFv constructs may serve as an excellent antibody format bi-functional antibody fragments that can be produced stably in the cytoplasm of E. coli.

• IMMUNE NETWORK
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• 제16권1호
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• pp.75-84
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• 2016

Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT⁺CD11c⁺cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

• 원예과학기술지
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• 제34권1호
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• pp.102-111
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• 2016

본 연구의 목적은 BrDSR(Drought Stress Resistance in B. rapa) 유전자의 기능을 명확히 밝히고, 배추에서 건조 스트레스 반응 유전자들을 분석하는데 있다. 내혼계배추('CT001')와 BrDSR 완전장(438bp의 오픈리딩프레임)을 지닌 pSL100 vector를 재료로 아그로박테리아를 이용한 배추 형질전환을 수행하였다. PCR 분석을 통해 4개체의 형질전환체를 확보하였고, 이들의 BrDSR 발현량은 건조 스트레스 조건에서 비형질전환체 대비 약 1.9-3.4배 정도 더 큰 것으로 분석되었다. 또한 표현형 분석에서도 BrDSR이 과발현된 형질전환체들은 건조 스트레스에 저항성을 보이며 정상적인 생장을 하였다. 기 구축된 건조 스트레스 반응 유전자의 상호발현 네트워크를 기반으로 BrDSR과 밀접한 관련이 있는 유전자들을 분석하기 위해 B. rapa 135K cDNA microarray 데이터를 분석하였다. 그 결과, 환경 스트레스와 관련하여 식물체에서 잎의 노화와 자가소화에 관련된 것으로 보고된 'dark inducible 2(DIN2, AT3G60140)'와 'autophagy 8h(ATG8H, AT3G06420)' 유전자가 확인되었다. 위 결과들을 근거로 BrDSR 유전자는 건조 스트레스에 대한 저항성 향상에 중요한 역할을 할 것으로 판단되었다.

• Animal Bioscience
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• 제35권7호
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• pp.975-988
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• 2022

Objective: In this study, we aimed to identify long non-coding RNAs (lncRNAs) that play important roles in starvation stress, analyze their functions, and discover potential molecular targets to alleviate starvation stress to provide a theoretical reference for subsequent in-depth research. Methods: We generated a piglet starvation stress animal model. Nine Yorkshire weaned piglets were randomly divided into a long-term starvation stress group (starved for 72 h), short-term starvation stress group (starved for 48 h), and the control group. LncRNA libraries were constructed using high-throughput sequencing of piglet ileums. Results: We obtained 11,792 lncRNAs, among which, 2,500 lncRNAs were novel. In total, 509 differentially expressed (DE)lncRNAs were identified in this study. Target genes of DElncRNAs were predicted via cis and trans interactions, and functional and pathway analyses were performed. Gene ontology functions and Kyoto encyclopedia of genes and genomes analysis revealed that lncRNA-targeted genes mainly participated in metabolic pathways, cellular processes, immune system processes, digestive systems, and transport activities. To reveal the mechanism underlying starvation stress, the interaction network between lncRNAs and their targets was constructed based on 26 DElncRNAs and 72 DEmRNAs. We performed an interaction network analysis of 121 DElncRNA-DEmRNA pairs with a Pearson correlation coefficient greater than 0.99. Conclusion: We found that MSTRG.19894.13, MSTRG.16726.3, and MSTRG.12176.1 might play important roles in starvation stress. This study not only generated a library of enriched lncRNAs in piglets, but its outcomes also provide a strong foundation to screen key lncRNAs involved in starvation stress and a reference for subsequent in-depth research.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4251-4256
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• 2015

Background: Exposure to cigarette may affect human health and increase risk of a wide range of diseases including pulmonary diseases, such as chronic obstructive pulmonary disease (COPD), asthma, lung fibrosis and lung cancer. However, the molecular mechanisms of pathogenesis induced by cigarettes still remain obscure even with extensive studies. With systemic view, we attempted to identify the specific gene modules that might relate to injury caused by cigarette smoke and identify hub genes for potential therapeutic targets or biomarkers from specific gene modules. Materials and Methods: The dataset GSE18344 was downloaded from the Gene Expression Omnibus (GEO) and divided into mouse cigarette smoke exposure and control groups. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to construct a gene co-expression network for each group and detected specific gene modules of cigarette smoke exposure by comparison. Results: A total of ten specific gene modules were identified only in the cigarette smoke exposure group but not in the control group. Seven hub genes were identified as well, including Fip1l1, Anp32a, Acsl4, Evl, Sdc1, Arap3 and Cd52. Conclusions: Specific gene modules may provide better understanding of molecular mechanisms, and hub genes are potential candidates of therapeutic targets that may possible improve development of novel treatment approaches.

• ALGAE
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• 제39권1호
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• pp.17-30
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• 2024

Red macroalga Pyropia yezoensis is a high valuable cultivated marine crop. Its acclimation to cold stress is especially important for long cultivation period across winter in coasts of warm temperate zone in East Asia. In this study, the response of P. yezoensis thalli to low temperature was analyzed on physiology and transcriptome level, to explore its acclimation mechanism to cold stress. The results showed that the practical photosynthesis activity (indicated by Φ_PSII and qP) was depressed and pigment allophycocyanin content was decreased during the cold stress of 48 h. However, the F_v/F_m and non-photochemical quenching increased significantly after 24 h, and the average growth rate of thalli also rebounded from 24 to 48 h, indicating a certain extent of acclimation to cold stress. On transcriptionally, the low temperature promoted the expression of differentially expressed genes (DEGs) related to carbohydrate metabolism and energy metabolism, while genes related to photosynthetic system were depressed. The increased expression of DEGs involved in ribosomal biogenesis and lipid metabolism which could accelerate protein synthesis and enhance the degree of fatty acid unsaturation, might help P. yezoensis thallus cells to cope with cold stress. Further co-expression network analysis revealed differential expression trends along with stress time, and corresponding hub genes play important roles in the systemic acquired acclimation to cold stress. This study provides basic mechanisms of P. yezoensis acclimation to cold temperature and may aid in exploration of functional genes for genetic breeding of economic macroalgae.

• IMMUNE NETWORK
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• 제10권2호
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• pp.55-63
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• 2010

Background: Cordyceps militaris has been used in traditional medicine to treat numerous diseases and has been reported to possess both antitumor and immunomodulatory activities in vitro and in vivo. However, the pharmacological and biochemical mechanisms of Cordyceps militaris extract (CME) on macrophages have not been clearly elucidated. In the present study, we examined how CME induces the production of proinflammatory cytokines, transcription factor, and the expression of co-stimulatory molecules. Methods: We confirmed the mRNA and protein levels of proinflammatory cytokines through RT-PCR and western blot analysis, followed by a FACS analysis for surface molecules. Results: CME dose dependently increased the production of NO and proinflammatory cytokines such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$, and $PGE_2$, and it induced the protein levels of iNOS, COX-2, and proinflammatory cytokines in a concentrationdependent manner, as determined by western blot and RT-PCR analysis, respectively. The expression of co-stimulatory molecules such as ICAM-1, B7-1, and B7-2 was also enhanced by CME. Furthermore, the activation of the nuclear transcription factor, NF-${\kappa}B$ in macrophages was stimulated by CME. Conclusion: Based on these observations, CME increased proinflammatory cytokines through the activation of NF-${\kappa}B$, further suggesting that CME may prove useful as an immune-enhancing agent in the treatment of immunological disease.

• IMMUNE NETWORK
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• 제10권3호
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• pp.92-98
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• 2010

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve pain, reduce fever and inhibit inflammation. NSAIDs function mainly through inhibition of cyclooxygenase (COX). Growing evidence suggests that NSAIDs also have immunomodulatory effects on T and B cells. Here we examined the effects of NSAIDs on the antigen presenting function of dendritic cells (DCs). Methods: DCs were cultured in the presence of aspirin or ibuprofen, and then allowed to phagocytose biodegradable microspheres containing ovalbumin (OVA). After washing and fixing, the efficacy of OVA peptide presentation by DCs was evaluated using OVA-specific CD8 and CD4 T cells. Results: Aspirin and ibuprofen at high concentrations inhibited both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the DCs generated in the presence of low concentrations of the drugs exhibit a profoundly suppressed capability to present MHC-restricted antigens. Aspirin and ibuprofen did not inhibit the phagocytic activity of DCs, the expression level of total MHC molecules and co-stimulatory molecules on DCs. Ibuprofen rather increased the expression level of total MHC molecules and co-stimulatory molecules on DCs. Conclusion: These results demonstrate that aspirin and ibuprofen inhibit the intracellular processing event of the phagocytosed antigen, and further suggest that prolonged administration of NSAIDs in high doses may impair the capability of DCs to present antigens in asiociation with MHC molecules.

• 한국문헌정보학회지
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• 제56권4호
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• pp.431-453
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• 2022

혐오는 타인에 대한 배타성이 집단적으로 표출된 것으로, 잘못된 대중적 인식을 통하여 양산되고 재생산된다. 이 연구는 우리사회에서 언급되고 있는 '혐오' 양상을 거시적으로 탐색하고자 1990년부터 2020년까지 발행된 뉴스데이터 17,867건을 대상으로 텍스트마이닝 기법을 활용하여 키워드 네트워크와 군집 분석을 수행하였다. 그리고 단어를 추출하기 전에 먼저 기사를 문장으로 분리하는 전처리 과정을 거쳐 '혐오', '편견', '차별'이라는 단어를 포함하고 있는 문장 총 52,520개를 추출하여 분석에 활용함으로써 '혐오'라는 단어와 인접한 단어들로 구성된 키워드 네트워크를 구축하였다. 수집한 뉴스데이터의 단어 동시출현빈도 분석 결과, 우리 사회에서 혐오와 관련되어 가장 빈번하게 등장하는 대상은 여성, 인종, 성소수자 등이며, 관련된 이슈는 이들 집단과 관련된 법과 범죄 등이었다. 키워드 네트워크 군집 분석 결과, 성별(41.4%), 소수자(28.7%), 인종·민족(15.1%), 선택적·이해관계적(8.5%), 정치·이념(5.7%), 환경·생존적(0.3%) 혐오 등 총 6개의 혐오 군집들이 발견되었다. 논의에서는 군집 분석 결과 구체적으로 드러나지 않은 혐오의 표적(대상)을 모두 추출하여 분석하였다.