• Journal of Computing Science and Engineering
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• 제11권4호
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• pp.111-120
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• 2017

Post-translational modifications (PTMs) of proteins play substantial roles in the gene regulation of cell physiological functions and in the generation of major diseases. However, the majority of existing studies only explored a certain PTM of proteins, while very few have investigated the PTMs of two or more domains and the effects of their interactions. In this study, after collecting data regarding a large number of breast cancer-related and validated PTMs, a sequence and domain analysis of breast cancer proteins was carried out using bioinformatics methods. Then, protein-protein interaction network-related tools were applied in order to determine the crosstalks between the PTMs of the proteins. Finally, statistical and functional analyses were conducted to identify more modification sites of domains and proteins that may interact with at least two or more PTMs. In addition to exploring the associations between the interactive effects of PTMs, the present study also provides important information that would allow biologists to further explore the regulatory pathways of biological functions and related diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.6989-6999
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• 2014

Colorectal cancer (CRC) is one of the major healthcare problems worldwide and its processes of genesis include a sequence of molecular pathways from adenoma to carcinoma. The discovery of microRNAs, a subset of regulatory non-coding RNAs, has added new insights into CRC diagnosis and management. Together with several causes of colorectal neoplasia, aberrant expression of oncomiRs (oncogenic and tumor suppressor miRNAs) in cancer cells was found to be indirectly result in up- or down-regulation of targeted mRNAs specific to tumor promoter or inhibitor genes. The study of miRNAs as CRC biomarkers utilizes expression profiling methods from traditional tissue samples along with newly introduced non-invasive samples of faeces and body fluids. In addition, miRNAs could be employed to predict chemo- and radio-therapy responses and be manipulated in order to alleviate CRC characteristics. The scope of this article is to provide a comprehensive review of scientific literature describing aberrantly expressed miRNAs, and consequently dysregulation of targeted mRNAs along with the potential role of miRNAs in CRC diagnosis and prognosis, as well as to summarize the recent findings on miRNA-based manipulation methods with the aim of advancing in anti-CRC therapies.

• IMMUNE NETWORK
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• 제12권4호
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• pp.148-154
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• 2012

Previously, we have reported that high mobility group box 1 (HMGB1), a proinflammatory mediator in sepsis, is released via the IFN-${\beta}$-mediated JAK/STAT pathway. However, detailed mechanisms are still unclear. In this study, we dissected upstream signaling pathways of HMGB1 release using various molecular biology methods. Here, we found that calcium/calmodulin-dependent protein kinase (CaM kinase, CaMK) is involved in HMGB1 release by regulating IFN-${\beta}$ production. CaMK inhibitor, STO609, treatment inhibits LPS-induced IFN-${\beta}$ production, which is correlated with the phosphorylation of interferon regulatory factor 3 (IRF3). Additionally, we show that CaMK-I plays a major role in IFN-${\beta}$ production although other CaMK members also seem to contribute to this event. Furthermore, the CaMK inhibitor treatment reduced IFN-${\beta}$ production in a murine endotoxemia. Our results suggest CaMKs contribute to HMGB1 release by enhancing IFN-${\beta}$ production in sepsis.

• BMB Reports
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• 제52권10호
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• pp.607-612
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• 2019

During meiosis, programmed double-strand breaks (DSBs) are repaired via recombination pathways that are required for faithful chromosomal segregation and genetic diversity. In meiotic progression, the non-homologous end joining (NHEJ) pathway is suppressed and instead meiotic recombination initiated by nucleolytic resection of DSB ends is the major pathway employed. This requires diverse recombinase proteins and regulatory factors involved in the formation of crossovers (COs) and non-crossovers (NCOs). In mitosis, spontaneous DSBs occurring at the G1 phase are predominantly repaired via NHEJ, mediating the joining of DNA ends. The Ku complex binds to these DSB ends, inhibiting additional DSB resection and mediating end joining with Dnl4, Lif1, and Nej1, which join the Ku complex and DSB ends. Here, we report the role of the Ku complex in DSB repair using a physical analysis of recombination in Saccharomyces cerevisiae during meiosis. We found that the Ku complex is not essential for meiotic progression, DSB formation, joint molecule formation, or CO/NCO formation during normal meiosis. Surprisingly, in the absence of the Ku complex and functional Mre11-Rad50-Xrs2 (MRX) complex, a large portion of meiotic DSBs was repaired via the recombination pathway to form COs and NCOs. Our data suggested that Ku complex prevents meiotic recombination in the elimination of MRX activity.

• 한국환경농학회:학술대회논문집
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• 한국환경농학회 2009년도 정기총회 및 국제심포지엄
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• pp.93-115
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• 2009

There are growing public concerns over crop and food safeties due to the elevated levels of heavy metals grown in contaminated soil. Heavy metals are classified as the chemical harmful risks for crop and food safety. With implementation of GAP, crop safety is controlled by many regulatory options for soil, irrigation water and fertilizers. Any attempt to retard the metal uptake by crops may be the best protocol to secure crop and food safety. This article reviews the management strategies for heavy metals in view of crop safety in Korea and demonstrates results from the field experiments to retard metal translocation from soil to crops by using chemical amendments and soil layer management methods. Major source of soil pollution by heavy metals has been related with mining activities. Risk assessment revealed that rice consumption and groundwater ingestion in the abandoned mining areas were the major exposure pathways for metals to human and the heavy metal showed the toxic effects on human health. Chemical amendments such as lime and slag retarded Cd uptake by rice (Oryza sativa L.) by increasing soil pH, lowering the phytoavailable Cd concentration in soil solution, immobilizing Cd in soil and converting the available Cd fractions into non-available fractions. The soil layer management methods decreased the Cd uptake by 76% and Pb by 60%. Either reversing the surface layer with subsurface layer or immobilization of metals with layer mixing with lime was considered to be the practical option for the in-situ remediation of the contaminated paddy soils. Combination of chemical soil amendments and layer management methods was efficient to retard the metal bioavailability and thus to secure crop safety for heavy metals. This protocol seems to be cheap, relatively easy to practice and practical in the agricultural fields. However, a long term monitoring work should be followed to verify the efficiency of this protocol.

• Biomolecules & Therapeutics
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• 제21권2호
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• pp.107-113
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• 2013

Plasminogen activator inhibitor-1 (PAI-1) is a member of serine protease inhibitor family, which regulates the activity of tissue plasminogen activator (tPA). In CNS, tPA/PAI-1 activity is involved in the regulation of a variety of cellular processes such as neuronal development, synaptic plasticity and cell survival. To gain a more insights into the regulatory mechanism modulating tPA/PAI-1 activity in brain, we investigated the effects of proteasome inhibitors on tPA/PAI-1 expression and activity in rat primary astrocytes, the major cell type expressing both tPA and PAI-1. We found that submicromolar concentration of MG132, a cell permeable peptide-aldehyde inhibitor of ubiquitin proteasome pathway selectively upregulates PAI-1 expression. Upregulation of PAI-1 mRNA as well as increased PAI-1 promoter reporter activity suggested that MG132 transcriptionally increased PAI-1 expression. The induction of PAI-1 downregulated tPA activity in rat primary astrocytes. Another proteasome inhibitor lactacystin similarly increased the expression of PAI-1 in rat primary astrocytes. MG132 activated MAPK pathways as well as PI3K/Akt pathways. Inhibitors of these signaling pathways reduced MG132-mediated upregulation of PAI-1 in varying degrees and most prominent effects were observed with SB203580, a p38 MAPK pathway inhibitor. The regulation of tPA/PAI-1 activity by proteasome inhibitor in rat primary astrocytes may underlie the observed CNS effects of MG132 such as neuroprotection.

• Animal Bioscience
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• 제34권6호
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• pp.975-984
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• 2021

Objective: Inbreeding depression of reproduction is a major concern in the conservation of native chicken genetic resources. Here, based on the successful development of strongly inbred (Sinb) and weakly inbred (Winb) Langshan chickens, we aimed to evaluate inbreeding effects on reproductive traits and identify candidate genes involved in inbreeding depression of reproduction in Langshan chickens. Methods: A two-sample t-test was performed to estimate the differences in phenotypic values of reproductive traits between Sinb and Winb chicken groups. Three healthy chickens with reproductive trait values around the group mean values were selected from each of the groups. Differences in ovarian and hypothalamus transcriptomes between the two groups of chickens were analyzed by RNA sequencing (RNA-Seq). Results: The Sinb chicken group showed an obvious inbreeding depression in reproduction, especially for traits of age at the first egg and egg number at 300 days (p<0.01). Furthermore, 68 and 618 differentially expressed genes (DEGs) were obtained in the hypothalamus and ovary between the two chicken groups, respectively. In the hypothalamus, DEGs were mainly enriched in the pathways related to vitamin metabolism, signal transduction and development of the reproductive system, such as the riboflavin metabolism, Wnt signaling pathway, extracellular matrix-receptor interaction and focal adhesion pathways, including stimulated by retinoic acid 6, serpin family F member 1, secreted frizzled related protein 2, Wnt family member 6, and frizzled class receptor 4 genes. In the ovary, DEGs were significantly enriched in pathways associated with basic metabolism, including amino acid metabolism, oxidative phosphorylation, and glycosaminoglycan degradation. A series of key DEGs involved in folate biosynthesis (gamma-glutamyl hydrolase, guanosine triphosphate cyclohydrolase 1), oocyte meiosis and ovarian function (cytoplasmic polyadenylation element binding protein 1, structural maintenance of chromosomes 1B, and speedy/RINGO cell cycle regulator family member A), spermatogenesis and male fertility (prostaglandin D2 synthase 21 kDa), Mov10 RISC complex RNA helicase like 1, and deuterosome assembly protein 1) were identified, and these may play important roles in inbreeding depression in reproduction. Conclusion: The results improve our understanding of the regulatory mechanisms underlying inbreeding depression in chicken reproduction and provide a theoretical basis for the conservation of species resources.

• 대한본초학회지
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• 제22권2호
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• pp.155-161
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• 2007

Objectives: Evidences suggests that Ginkgo biloba, a widely used traditional medicine, shows a hypoglycemic effect. Thus, we investigatd the effect of G. biloba extract (GB) on glucose uptake in L6 rat skeletal muscle cells. Method : Effect of GB on glucose uptake and phosphatidylinositol (PI) 3-kinase activity were assessed using Glucose uptake assay and PI 3-kinase assay, respectively. Also, AMP-activated protein kinase (AMPK), p38 mitogen activated protein kinase (p38 MAPK) expression were identified by Western blot. Results : Glucose uptake assay revealed that GB increased glucose uptake about 2.5-fold compared to thecontrol. GB stimulated the activity of PI 3-kinase which is a major switch element on the glucose uptake pathway. About a 6.5-fold increase in activity of PI 3-kinase was observed with GB. We then assessed the activity of AMPK, another regulatory molecule on the glucose uptake pathway. The result was that GB increased the phosphorylation level of both AMPK ${\alpha}$l and ${\alpha}$2. The activity of p38 MAPK, a downstream mediator of AMPK, was also increased by CB. Conclusion : These results suggest that GB may stimulate glucose uptake through both PI 3-kinase and AMPK mediated pathways in L6 skeletal muscle cells thereby contributing to glucose homeostasis.

• Molecular & Cellular Toxicology
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• 제4권3호
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• pp.260-266
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• 2008

Recently, there has been scientific discussion on the utility of -omics techniques such as genomics, proteomics, and metabolomics within toxicological research and mechanism-based risk assessment. Toxicogenomics is a novel approach integrating the expression analysis of genes (genomic) or proteins (proteomic) with traditional toxicological methods. Since 1999, the toxicogenomic approach has been extensively applied for regulatory purposes in order to understand the potential toxic mechanisms that result from chemical compound exposures. Therefore, this article's purpose was to consider the utility of toxicogenomic profiles for improved risk assessment, explore the current limitations in applying toxicogenomics to regulation, and finally, to rationalize possible avenues to resolve some of the major challenges. Based on many recent works, the significant impact toxicogenomic techniques would have on human health risk assessment is better identification of toxicity pathways or mode-of-actions (MOAs). In addition, the application of toxicogenomics in risk assessment and regulation has proven to be cost effective in terms of screening unknown toxicants prior to more extensive and costly experimental evaluation. However, to maximize the utility of these techniques in regulation, researchers and regulators must resolve many parallel challenges with regard to data collection, integration, and interpretation. Furthermore, standard guidance has to be prepared for researchers and assessors on the scientifically appropriate use of toxicogenomic profiles in risk assessment. The National Institute of Toxicological Research (NITR) looks forward to an ongoing role as leader in addressing the challenges associated with the scientifically sound use of toxicogenomics data in risk assessment.

• 정신신체의학
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• 제7권2호
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• pp.149-157
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• 1999

인간은 에너지 섭취와 소모에 있어 변동이 심한 편이지만 비교적 일정한 체중을 유지하고 적절하게 섭식행동을 조절한다. 그러나 이러한 조절기전에 문제가 발생하면 비만이나 그 이외의 다른 섭식장애를 일으키게 되며 다양한 후유증을 야기한다. 본 논문에서는 최근에 소개되기 시작한 호르몬인 leptin이 섭식의 조절과 에너지의 항상성을 조절하는데 있어 어떻게 중요한 작용을 하게되는지 조사하여 주로 정신과 영역에서 관심을 기울일 만한 부분에 대해 고찰하고자 한다. Leptin이 처음 발견되었을 때 그 역할은 주로 음식의 섭취를 제한하고 에너지의 소모를 증가시키는 호르몬으로 소개되었지만, 점차 그 이외의 다른 신체 기능 즉, 생식주기나 신경대분기계에도 영향을 미치는 것으로 보고되면서 정선과 영역에서 차지하는 비중도 확대되고 있다. 그러나 leptin의 작용기전은 매우 복잡하며 많은 부분이 아직도 불분명한 상태에 있다. 이에 저자들은 중추신경계에서 현재까지 알려진 leptin의 작용기전에 대해 살펴보고 섭식과 관련된 그 밖의 다른 신경전달물질들과의 상호작용 그리고 섭식장애와의 관련성에 대해서 최근 문헌들을 조사하여 함께 고찰하고자 한다.