• Title/Summary/Keyword: Biomarker protein

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Synthesis and evaluation of inhibitors for Polo-box domain of Polo-like kinase 1

  • Eun Kyoung Ryu
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.6 no.2
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    • pp.139-145
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    • 2020
  • Polo-like kinase 1 (Plk1) is a key protein in mitosis and has been validated as a target for tumor therapy. It is well known to highly overexpress in many kinds of tumor, which has been implicated as a potential biomarker for tumor treatment and diagnosis. Plk1 consists of two domains, the N-terminus kinase domain and the C-terminus polo-box domain (PBD). The inhibitors have been developed for PBD of Plk1, which were shown a high level of affinity and selectivity for Plk1 that led to mitotic arrest and apoptotic cell death. This review discusses the inhibitors for PBD of Plk1 that are suitable for in vivo tumor treatment. They can be further extended for developing in vivo imaging probes for early diagnosis of tumor.

Prediction of Lung Cancer Based on Serum Biomarkers by Gene Expression Programming Methods

  • Yu, Zhuang;Chen, Xiao-Zheng;Cui, Lian-Hua;Si, Hong-Zong;Lu, Hai-Jiao;Liu, Shi-Hai
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9367-9373
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    • 2014
  • In diagnosis of lung cancer, rapid distinction between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) tumors is very important. Serum markers, including lactate dehydrogenase (LDH), C-reactive protein (CRP), carcino-embryonic antigen (CEA), neurone specific enolase (NSE) and Cyfra21-1, are reported to reflect lung cancer characteristics. In this study classification of lung tumors was made based on biomarkers (measured in 120 NSCLC and 60 SCLC patients) by setting up optimal biomarker joint models with a powerful computerized tool - gene expression programming (GEP). GEP is a learning algorithm that combines the advantages of genetic programming (GP) and genetic algorithms (GA). It specifically focuses on relationships between variables in sets of data and then builds models to explain these relationships, and has been successfully used in formula finding and function mining. As a basis for defining a GEP environment for SCLC and NSCLC prediction, three explicit predictive models were constructed. CEA and NSE are requentlyused lung cancer markers in clinical trials, CRP, LDH and Cyfra21-1 have significant meaning in lung cancer, basis on CEA and NSE we set up three GEP models-GEP 1(CEA, NSE, Cyfra21-1), GEP2 (CEA, NSE, LDH), GEP3 (CEA, NSE, CRP). The best classification result of GEP gained when CEA, NSE and Cyfra21-1 were combined: 128 of 135 subjects in the training set and 40 of 45 subjects in the test set were classified correctly, the accuracy rate is 94.8% in training set; on collection of samples for testing, the accuracy rate is 88.9%. With GEP2, the accuracy was significantly decreased by 1.5% and 6.6% in training set and test set, in GEP3 was 0.82% and 4.45% respectively. Serum Cyfra21-1 is a useful and sensitive serum biomarker in discriminating between NSCLC and SCLC. GEP modeling is a promising and excellent tool in diagnosis of lung cancer.

N-glycoproteomic analysis of human follicular fluid during natural and stimulated cycles in patients undergoing in vitro fertilization

  • Lim, Hee-Joung;Seok, Ae Eun;Han, Jiyou;Lee, Jiyeong;Lee, Sungeun;Kang, Hee-Gyoo;Cha, Byung Heun;Yang, Yunseok
    • Clinical and Experimental Reproductive Medicine
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    • v.44 no.2
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    • pp.63-72
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    • 2017
  • Objective: Hyperstimulation methods are broadly used for in vitro fertilization (IVF) in patients with infertility; however, the side effects associated with these therapies, such as ovarian hyperstimulation syndrome (OHSS), have not been well studied. N-glycoproteomes are subproteomes used for the remote sensing of ovarian stimulation in follicular growth. Glycoproteomic variation in human follicular fluid (hFF) has not been evaluated. In this study, we aimed to identify and quantify the glycoproteomes and N-glycoproteins (N-GPs) in natural and stimulated hFF using label-free nano-liquid chromatography/electrospray ionization-quad time-of-flight mass spectrometry. Methods: For profiling of the total proteome and glycoproteome, pooled protein samples from natural and stimulated hFF samples were selectively isolated using hydrazide chemistry to obtain the total proteomes and glycoproteomes. N-GPs were validated by the consensus sequence N-X-S/T (92.2% specificity for the N-glycomotif at p<0.05). All data were compared between natural versus hyperstimulated hFF samples. Results: We detected 41 and 44 N-GPs in the natural and stimulated hFF samples, respectively. Importantly, we identified 11 N-GPs with greater than two-fold upregulation in stimulated hFF samples compared to natural hFF samples. We also validated the novel N-GPs thyroxine-binding globulin, vitamin D-binding protein, and complement proteins C3 and C9. Conclusion: We identified and classified N-GPs in hFF to improve our understanding of follicular physiology in patients requiring assisted reproduction. Our results provided important insights into the prevention of hyperstimulation side effects, such as OHSS.

Proteome in Toxicological Assessment of Endocrine Disrupting Chemicals (프로테오믹스를 이용한 내분비계 교란물질 환경독성 연구)

  • 김호승;계명찬
    • Korean Journal of Environmental Biology
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    • v.21 no.2
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    • pp.87-100
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    • 2003
  • It is important to understand the potential human health implications of exposure to environmental chemicals that may act as hormonally active agents. It is necessary to have an understanding of how pharmaceutical and personal care products and other chemicals affect the ecosystem of our planet as well as human health. Endocrine disruption is defined as the ability of a chemical contaminating the workplace or the environment to interfere with homeostasis, development, reproduction, and/or behavior in a living organism or it's offspring. Certain classes of environmentally persistent chemicals such as polychlorinated biphenyls (PCBs), dioxins, furans, and some pesticides can adversely effect the endocrine systems of aquatic life and terrestrial wildlife. Research continues to support the theory of endocrine disruption. However, endocrine disruption researches have been applied to proteomics poorly. Proteomics can be defined as the systematic analysis of proteins for their identity, quantity and function. It could increase the predictability of early drug development and identify non-invasive biomarkers of tonicity or efficacy. Proteome analysis is most commonly accomplished by the combination of two-dimensional gel electrophoresis (2D/E) and MALDI-TOF mass spectrometry (MS) sr protein chip array and SELDI-TOF MS. Proteomics have an opportunity to play an important role in resolving the question of what role endocrine disruptors play in initiating human disease. Proteomics can also play an imfortant role in the evaluation of the risk assessment and use of risk management and risk communication tools required to address public health concerns related to notions of endocrine disruptors. Understanding the need for the proteomics and possessing knowledge of the developing biomakers used to abbess endocrine activity potential will he essential components relevant to the topic of endocrine disruptors.

Analysis of Human Serum Amyloid A-1 Concentrations Using a Lateral Flow Immunoassay with CdSe/ZnS Quantum Dots (Human Serum Amyloid A-1 단백질 농도 분석을 위한 CdSe/ZnS 양자점 기반의 Lateral Flow Immunoassay 방법 개발)

  • Fajri, Aidil;Goh, Eunseo;Lee, Sanghyuk;Lee, Hye Jin
    • Applied Chemistry for Engineering
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    • v.30 no.4
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    • pp.429-434
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    • 2019
  • A lateral flow immunoassay platform utilizing antibody functionalized water soluble CdSe/ZnS semiconductor quantum dots (QDs) was developed for the analysis of human serum amyloid A-1 (hSAA1) in a buffer solution. hSAA1 was chosen as a target protein because it is regarded as a potential biomarker associated with early diagnosis and prognosis in patients of lung cancer. The immunoassay strip on a nitrocellulose membrane was fabricated by spraying two lines composed of a test line with a monoclonal antibody against hSAA1 (10G1) (anti hSAA1) and a control line of anti-chicken IgY. While the CdSe/ZnS QDs synthesized in an organic phase were transferred to a water phase by ligand exchange using carboxylic acid modified alkane thiol. The QDs was then conjugated to monoclonal antibody against hSAA1 (14F8) [anti hSAA1 (14F8)] and used as a fluorescent detection probe. The sequential lateral flow of hSAA1 in different concentration and QDs-anti hSAA1 (14F8) complex allowed to form the surface sandwich complex of anti hSAA1 (10G1)/hSAA1/QD-anti hSAA1 (14F8), which was then analyzed using fluorescence microscope. A 100 nM concentration of hSAA1 protein can be detected by naked eyes under an optimized lateral flow buffer condition with a sensing time of 5 mins.

Iron deficiency in Retired Workers exposed to Mineral dust with Chronic Obstructive Pulmonary Disease (만성폐쇄성폐질환을 동반한 광물성분진 노출 이직근로자의 철 결핍)

  • Lee, Jong Seong;Shin, Jae Hoon;Baek, Jin Ee;Jeong, Ji Yeong;Kim, Hyeong Geun;Choi, Byung-Soon
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.29 no.1
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    • pp.42-49
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    • 2019
  • Objective: Chronic obstructive pulmonary disease(COPD) is characterized by persistent airflow limitations associated with chronic inflammatory response due to noxious particles or gases in the lung. Iron deficiency is associated with chronic inflammation, such as COPD. The aim of this study was to evaluate the relationship among iron deficiency, iron homeostasis, and inflammation in retired miners with COPD. Methods: The serum levels of ferritin, soluble transferrin receptor(sTfR), and transferrin saturation(TSat) as biomarkers for iron deficiency and high-sensitivity C-reactive protein(hsCRP) as a biomarker for inflammation and hepcidin as a biomarker for iron homeostasis were measured in 93 male subjects. Iron deficiency was defined as any one or more of (1) sTfR>28.1 nmol/L, (2) TSat<16%, and (3) ferritin< $12{\mu}g/L$. Results: Iron deficiency was found 28% of the study subjects. Median levels of serum hsCRP was significantly increased related to airflow limitation of COPD(GOLD 1, $0.09{\mu}g/dL$ vs. GOLD 2, $0.17{\mu}g/dL$ vs. GOLD $3{\leq}$, $0.30{\mu}g/dL$, p=0.010), and was positively correlated with hepcidin(p=0.009). Mean level of serum hepcidin was lower in COPD subjects with iron deficiency(p=0.004) and serum levels of hepcidin was negatively correlated with %$FEV_1$ predicted(p=0.030). Conclusions: These results suggest that high serum levels of hepcidin are related to severe airflow limitation or inflammation and can decrease iron availability, regardless of iron status.

The Effect of Trichosanthes Kirilowii Maximowicz Extract and Trichosanthes Kirilowii Maximowicz Cheonghyeol Plus on Anti-Inflammatory Factor Expression in Human Umbilical Vein Endothelial Cells (HUVECs) (과루인 및 과루인청혈플러스가 인간 탯줄 정맥 내피 세포(Human umbilicl vein endothelial cells, HUVECs)에서 염증인자 발현 억제에 미치는 영향)

  • Kim, Hae-yoong;Seol, In-chan;Yoo, Ho-ryong;Kim, Yoon-sik
    • The Journal of Internal Korean Medicine
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    • v.43 no.4
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    • pp.514-528
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    • 2022
  • Objective: To examine the effects of Trichosanthes kirilowii Maximowicz extract (TE) and Trichosanthes kirilowii Maxi mowicz Cheonghyeol Plus Phellinus linteus Cheonghyeol plus (TCP) on anti-inflammatory factor expression in human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were activated with TNF-α and then treated with TE and TCP. The expression levels were then measured for intracellular genes (KLF2, eNOS, MCP-1, ICAM-1, and VCAM-1), proteins (KLF2, eNOS, MCP-1, ICAM-1, VCAM-1, ERK, and JNK, p38), and extracellular biomarkers (ICAM-1, VCAM-1, and MCP-1). Results: 1. TCP at concentrations of 100 ㎍/mL or greater significantly increased the expression of KLF2 and eNOS intracellular genes and significantly decreased the expression of ICAM-1, VCAM-1, and MCP-1 genes compared to the control group. 2. TCP at concentrations of 100 ㎍/mL or greater significantly increased the expression of KLF2, eNOS proteins compared to the control group, and significantly reduced the expression of VCAM-1, ICAM-1, MCP-1, ERK, and p38 proteins. However, JNK protein phosphorylation showed no significant change compared to the control group. 3. TCP at concentrations of 100 ㎍/mL or more significantly decreased the production of MCP-1, ICAM-1, and VCAM-1 extracellular biomarkers compared to the control group. 4. TE at a concentration of 100 ㎍/mL did not cause any significant change in the expression of intracellular genes or proteins, in the production of the extracellular biomarker MCP-1, or in the amount of JNK protein compared to the control group. Other intracellular genes, proteins, and extracellular biomarker expression showed the same trend as observed with TCP exposure. Conclusion: This study experimentally confirmed that TE and TCP could be effective in preventing or inhibiting various inflammatory vascular diseases due to their anti-inflammatory effects.

Global Absolute Quantitation of Proteins in Human Whole Saliva by nLC-QIMS-TOF Employing MSE

  • Cho, Ha Ra;Jin, Sung Giu;Park, Jun Seo;Kim, Han Sol;Choi, Yong Seok
    • Mass Spectrometry Letters
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    • v.8 no.4
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    • pp.114-118
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    • 2017
  • While saliva can be considered as good biological fluid for monitoring biomarkers due to many advantages including its communication with blood and the non-invasive nature during its sampling, its applications to that purpose is still limited. As a part of efforts to expand the applications of saliva to the protein biomarker research, we carried out global absolute quantitation of proteins in human whole saliva (WS) by bottom-up proteomics techniques mainly based on nLC-Q-IMS-TOF employing $MS^E$. From the analyses of a pooled WS sample collected from 22 healthy Korean volunteers, 93 proteins ranging from $5.89{\times}10^1ng/mL$ (immunoglobulin heavy chain) to $1.59{\times}10^4ng/mL$ (${\alpha}-amylase$ 1) were confirmed. For the validation of the present results, human serum albumin in the same sample was quantitated by ELISA and its result was compared with that from the nLC-Q-IMS-TOF study. As a result, there was no significant difference between two results from individual approaches ($1.18{\times}10^4{\pm}0.03{\times}10^4 ng/mL$ from nLC-Q-IMS-TOF experiments vs. $1.23{\times}10^4{\pm}0.07{\times}10^4ng/mL$ from ELISA experiments, n=3, p=0.309). To our knowledge, this is the first global absolute quantitation of proteins in human whole saliva and information from the present study can be widely used as the first level reference for the discovery of new protein biomarkers from human whole saliva as well as for quantitative applications of human whole saliva proteins.

Long non-coding RNA: its evolutionary relics and biological implications in mammals: a review

  • Dhanoa, Jasdeep Kaur;Sethi, Ram Saran;Verma, Ramneek;Arora, Jaspreet Singh;Mukhopadhyay, Chandra Sekhar
    • Journal of Animal Science and Technology
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    • v.60 no.10
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    • pp.25.1-25.10
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    • 2018
  • The central dogma of gene expression propounds that DNA is transcribed to mRNA and finally gets translated into protein. Only 2-3% of the genomic DNA is transcribed to protein-coding mRNA. Interestingly, only a further minuscule part of genomic DNA encodes for long non-coding RNAs (lncRNAs) which are characteristically more than 200 nucleotides long and can be transcribed from both protein-coding (e.g. H19 and TUG1) as well as non-coding DNA by RNA polymerase II. The lncRNAs do not have open reading frames (with some exceptions), 3`-untranslated regions (3'-UTRs) and necessarily these RNAs lack any translation-termination regions, however, these can be spliced, capped and polyadenylated as mRNA molecules. The flexibility of lncRNAs confers them specific 3D-conformations that eventually enable the lncRNAs to interact with proteins, DNA or other RNA molecules via base pairing or by forming networks. The lncRNAs play a major role in gene regulation, cell differentiation, cancer cell invasion and metastasis and chromatin remodeling. Deregulation of lncRNA is also responsible for numerous diseases in mammals. Various studies have revealed their significance as biomarkers for prognosis and diagnosis of cancer. The aim of this review is to overview the salient features, evolution, biogenesis and biological importance of these molecules in the mammalian system.

CHANGING OF RGS TRANSCRIPTS LEVELS BY LOW-DOSE-RATE IONIZING RADIATION IN MOUSE TESTIS

  • Kim, Tae-Hwan;Baik, Ji Sue;Heo, Kyu;Kim, Joong Sun;Lee, Ki Ja;Rhee, Man Hee;Kim, Sung Dae
    • Journal of Radiation Protection and Research
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    • v.40 no.3
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    • pp.187-193
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    • 2015
  • Deleterious effects of high dose radiation exposure with high-dose-rate are unarguable, but they are still controversial in low-dose-rate. The regulator of G-protein signaling (RGS) is a negative regulator of G protein-coupled receptor (GPCR) signaling. In addition, it is reported that irradiation stress led to GPCR-mediated mitogen-activated protein kinase (MAPK) and phosphotidylinositol 3-kinase (PI3-k) signaling. The RGS mRNA expression profiles by whole body radiation with low-dose-rate has not yet been explored. In the present study, we, therefore, examined which RGS was modulated by the whole body radiation with low-dose-rate ($3.49mGy{\cdot}h^{-1}$). Among 16 RGS expression tested, RGS6, RGS13 and RGS16 mRNA were down-regulated by low-dose-rate irradiation. This is the first report that whole body radiation with low-dose-rate can modulate the different RGS expression levels. These results are expected to reveal the potential target and/or the biomarker proteins associated with male testis toxicity induced by low-dose-rate irradiation, which might contribute to understanding the mechanism beyond the testis toxicity.