• Nutrition Research and Practice
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• v.16 no.6
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• pp.729-744
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• 2022

BACKGROUND/OBJECTIVES: 4-Hydroxy-2-nonenal (HNE) is a biomarker for oxidative stress to induce inflammation. Methionine is an essential sulfur-containing amino acid with antioxidative activity. On the other hand, the evidence on whether and how methionine can depress HNE-derived inflammation is lacking. In particular, the link between the regulation of the nuclear factor-κB (NF-κB) signaling pathway and methionine intake is unclear. This study examined the link between depression from HNE accumulation and the anti-inflammatory function of ⳑ-methionine in rats. MATERIALS/METHODS: Male Wistar rats (3-week-old, weighing 70-80 g) were administered different levels of ⳑ-methionine orally at 215.0, 268.8, 322.5, and 430.0 mg/kg body weight for two weeks. The control group was fed commercial pellets. The hepatic HNE contents and the protein expression and mRNA levels of the inflammatory mediators were measured. The interleukin-10 (IL-10) and glutathione S-transferase (GST) levels were also estimated. RESULTS: Compared to the control group, hepatic HNE levels were reduced significantly in all groups fed ⳑ-methionine, which were attributed to the stimulation of GST by ⳑ-methionine. With decreasing HNE levels, ⳑ-methionine inhibited the activation of NF-κB by up-regulating inhibitory κBα and depressing phosphoinositide 3 kinase/protein kinase B. The mRNA levels of the inflammatory mediators (cyclooxygenase-2, interleukin-1β, interleukin-6, inducible nitric oxide synthase, tumor necrotic factor alpha) were decreased significantly by ⳑ-methionine. In contrast, the protein expression of these inflammatory mediators was effectively down regulated by ⳑ-methionine. The anti-inflammatory action of ⳑ-methionine was also reflected by the up-regulation of IL-10. CONCLUSIONS: This study revealed a link between the inhibition of HNE accumulation and the depression of inflammation in growing rats, which was attributed to ⳑ-methionine availability. The anti-inflammatory mechanism exerted by ⳑ-methionine was to inhibit NF-κB activation and to up-regulate GST.

• Tuberculosis and Respiratory Diseases
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• v.66 no.6
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• pp.444-450
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• 2009

Background: Biomarkers for cancer have several potential clinical uses, including the following: early cancer detection, monitoring for recurrence prognostication, and risk stratification. However, no biomarker has been shown to have adequate sensitivity and specificity. Many investigators have tried to validate biomarkers for the early detection and recurrence of lung cancer. To evaluate plasma G-CSF as such a biomarker, protein levels were measured and were found to correlate with the clinicopathological features of primary lung tumors. Methods: Between December 2006 and May 2008, 100 patients with histologically-validated primary lung cancer were enrolled into this study. To serve as controls, 127 healthy volunteers were enrolled into this study. Plasma G-CSF levels were measured in lung cancer patients using the sandwich ELISA system (R & D inc.) prior to treatment. Results: The mean plasma G-CSF levels were 12.2$\pm$0.3 pg/mL and 46.0$\pm$3.8 pg/mL (mean$\pm$SE) in the normal and in the cancer groups, respectively. In addition, plasma G-CSF levels were higher in patients with early lung cancer than in healthy volunteers (p<.001). Plasma G-CSF levels were higher in patients who were under 65 years old or smokers. Within the cancer group, plasma G-CSF levels were higher in patients with non small cell lung cancer than in patients with small cell lung cancer (p<.05). Overall, plasma G-CSF levels were shown to increase dependent upon the type of lung cancer diagnsosed. In the order from highest to lowest, the levels of plasma G-CSF tended to decrease in the following order: large cell carcinoma, squamous cell carcinoma, adenocarcinoma, and bronchioloalveolar carcinoma. Plasma G-CSF levels tended to be higher in patients with advanced TNM stage than in localized TNM stage (I, II

• Reproductive and Developmental Biology
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• v.32 no.4
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• pp.211-215
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• 2008

The HMG box containing protein (HBP) has a high mobility group domain and involved in the regulation of proliferation and differentiation of tissues. We screened HBP2 in glioblastoma using Suppression Subtractive Hybridization (SSH) and isolated human spermatogonial stem cell-like cells (hSSC-like cells) derived from patients of nonobstructive azoospermia (NOA). Expression of HBP2 was analyzed by RT-PCR in undifferentiated stem cells (human Embryonic Stem Cells, hSSC-like cells 2P) and spontaneous differentiated stem cells (hSSC-like cells 4P). It was overexpressed in hESC and hSSC-like cells 2P but not in hSSC-like cells 4P. Also, the expression level of HBP2 was downregulated in colon tumor tissues compared to normal tissues. Specifically in synchronized WI-38 cells, HBP2 was highly upregulated until the G1 phase of the cell cycle and gradually decreased during the S phase. Our results suggest that HBP2 was downregulated during the spontaneous differentiation of hSSC-like cells. HBP2 was differently expressed in colon tissues and was related to G1-progression in WI-38 cells. It may playa role in the maintenance of an undifferentiated hSSC-like cell state and transits from G1 to S in WI-38 cells. This research was important that it identified a biomarker for an undifferentiated state of hSSC-like cells and characterized its involvement to arrest during cell cycle in colon cancer.

• Korean Journal of Environmental Biology
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• v.33 no.4
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• pp.433-440
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• 2015

The Apostichopus japonicus is an important species in some Asia countries including Korea, China and Japan. The purpose of the present study was to investigate the differential gene expression of heat shock protein90 (Hsp90) and ferritin as a biomarker for the thermal stress during water temperature rising in the sea cucumber, A. japonicus. The A. japonicus (1.4 g) was cultured in incubator of separate temperature ($15^{\circ}C$, $20^{\circ}C$, $25^{\circ}C$ and $30^{\circ}C$) for each 0, 3, 6, 12, 24, 48 hours. The mRNA expression levels of Hsp90 and ferritin were examined using RT-PCR assay. Results showed that, the expression of Hsp90 mRNA was not significantly changed at $15^{\circ}C$. The expression of Hsp90 mRNA was significantly increased at high temperature such as $20^{\circ}C$ and $25^{\circ}C$. Furthermore, Hsp90 mRNA was early increased at $25^{\circ}C$ than $20^{\circ}C$. The ferritin mRNA was similar expression pattern with Hsp90. But, Hsp90 mRNA was more sensitive than ferritin mRNA at high thermal stress. These results indicate that Hsp90 and ferritin mRNAs were involved in the temperature changes response and may be play an important role in mediating the thermal stress in A. japonicas.

• Biomedical Science Letters
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• v.22 no.1
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• pp.18-23
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• 2016

Ultraviolet (UV) irradiation induces cellular damage. A variety of cellular responses for repairing cellular damage including DNA damage occur after UV irradiation. During the repair processes, expression and activation of various molecules are regulated depending on the types of cellular damage. Parkin is an E3 ligase and act as a tumor suppressor. Recently, it has been reported that Parkin is involved in the DNA repair process. In the current study, we investigated whether UVB irradiation influences expression of Parkin. Parkin expression transiently decreased after UVB irradiation both at the mRNA and protein levels, but returned to normal levels thereafter. Taken together with cell viability data, Parkin expression is down-regulated during UVB-induced suppression of cell growth and is increased again in accordance with recovery of UVB-induced cell growth inhibition. However, Parkin overexpression or knockdown did not influence UVB-induced cell growth inhibition and recovery. We propose that Parkin could be a useful molecular marker for evaluating conditions of cells after UVB irradiation.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3509-3514
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• 2013

The prognostic value of the fibroblast growth factor-inducible 14 (Fn14) expression in hepatocellular carcinoma (HCC) is unknown. Real-time PCR (RT-PCR), western blot assays and immunohistochemistry analysis were here performed in order to compare Fn14 expressios in paired liver samples of HCC and normal liver tissue. Most of the tumor tissues expressed significantly higher levels of Fn14 compared to adjacent non-tumor tissues, with Fn14High accounting for 54.6% (142/260) of all patients. The Pearson ${\chi}^2$ test indicated that Fn14 expression was closely associated with serum alpha fetal protein (AFP) (P=0.002) and tumor number (p=0.019). Univariate and multivariate analyses revealed that along with tumor diameter and portal vein tumor thrombosis (PVTT ) type, Fn14 was an independent prognostic factor for both overall survival (OS) (HR=1.398, p=0.008) and recurrence (HR=1.541, p=0.001) rates. Fn14 overexpression HCC correlated with poor surgical outcome, and this molecule may be a candidate biomarker for prognosis as well as a target for therapy.

• Clinical and Experimental Pediatrics
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• v.59 no.7
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• pp.298-302
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• 2016

Purpose: Recent reports showed that plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) could be a useful biomarker of intravenous immunoglobulin (IVIG) unresponsiveness and coronary artery lesion (CAL) development in Kawasaki disease (KD). The levels of these peptides are critically influenced by age; hence, the normal range and upper limits for infants and children are different. We performed an age-adjusted analysis of plasma NT-proBNP level to validate its clinical use in the diagnosis of KD. Methods: The data of 131 patients with KD were retrospectively analyzed. The patients were divided into 2 groups-group I (high NT-proBNP group) and group II (normal NT-proBNP group)-comprising patients with NT-proBNP concentrations higher and lower than the 95th percentile of the reference value, respectively. We compared the laboratory data, responsiveness to IVIG, and the risk of CAL in both groups. Results: Group I showed significantly higher white blood cell count, absolute neutrophil count, C-reactive protein level, aspartate aminotransferase level, and troponin-I level than group II (P<0.05). The risk of CAL was also significantly higher in group I (odds ratio, 5.78; P=0.012). IVIG unresponsiveness in group I was three times that in group II (odds ratio, 3.35; P= 0.005). Conclusion: Age-adjusted analysis of plasma NT-proBNP level could be helpful in predicting IVIG unresponsiveness and risk of CAL development in patients with KD.

• Korean Journal of Food Science and Technology
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• v.39 no.5
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• pp.558-563
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• 2007

This study was conducted to analyze the cytotoxic effects of butylated hydroxytoluene (BHT) and propyl gallate (PG) in WB-F344 rat liver epithelial cells. Here we measured the inhibition level of gap junctional intercellular communication (GJIC) and elucidated the relationships between GJIC and mitogen-activated protein kinases (MAPKs) such as ERK, JNK, and p38. The cytotoxicities of BHT and PG appeared at concentrations of 1.0mM and 0.25mM, respectively, in the WB-F344 cells; and GJIC inhibition, which was analyzed by a scrape-loading/dye transfer assay and Western blotting analysis, appeared at 0.6mM for BHT and 0.1mM for PG, respectively. Also, the phosphorylations of Cx43, ERK, JNK, and p38 increased in dose-dependent manners. This suggests that BHT and PG treatments inhibited GJIC by the phosphorylation of MAPKs prior to cell damage.

• Journal of fish pathology
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• v.33 no.1
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• pp.35-43
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• 2020

Hypoxia is a serious problem in the marine ecosystem causing a decline in aquatic resources. MicroRNAs (miRNAs) regulate the expression of genes through binding to the corresponding sequences of their target mRNAs. Especially, miRNAs in the cytoplasm can be secreted into body fluids, which called circulating miRNAs, and the availability of circulating miRNAs as biomarkers for hypoxia has been demonstrated in mammals. However, there has been no report on the hypoxia-mediated changes in the circulating miRNAs in fish. miR-210 is known as the representative hypoxia-responsive circulating miRNA in mammals. To know whether fish miR-210 also respond to hypoxia, we analyzed the change of circulating miR-210 quantity in the serum of olive flounder (Paralichthys olivaceus) in response to hypoxia. The expression of hypoxia related genes, hypoxia inducible factor 1α (HIF-1α) and the heat shock protein 90α (HSP90α) was also analyzed. Similar to the reports from mammals, miR-210-5p and miR-210-3p were significantly increased in the serum of olive flounder in response to hypoxia, suggesting that circulating miR-210 levels in the serum can be used as a noninvasive prognostic biomarker for fish suffered hypoxia. The target genes of miR-210 were related to various biological processes, which explains the major regulatory role of miR-210 in response to hypoxia. The expression of HIF-1α and HSP90α in the tissues was also up-regulated by hypoxia. Considering the critical role of HIF-1α in miR-210 expression and HSP90 in miRNAs function, the present up-regulation of HIF-1α and HSP90α might be related to the increase of circulatory miR-210, and the interaction mechanism among HIF-1α, HSP90α, and hypoxia-responsive microRNAs in fish should be further studied.

• Journal of Microbiology and Biotechnology
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• v.20 no.6
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• pp.959-967
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• 2010

Down syndrome (DS) is an abnormality of the 21st chromosome that commonly occurs in children born to older women. Thus, amniotic fluid (AF) is usually collected from such women for prenatal diagnosis. This study analyzed human AF supernatants (AFS) using a mass spectrometric (MS) approach to search for candidate biomarkers of a DS pregnancy. The AFS were collected from older pregnant women at weeks 16-18 of their gestation by amniocentesis for cytogenetic analysis. The AFS from the pregnancies carrying DS (n=4) or chromosomally normal (n=6) fetuses, as revealed by the cytogenetic analysis, were then subjected to global protein profiling based on liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Affinity chromatography was also applied prior to the LC-ESI-MS/MS to minimize the masking effect of highly abundant albumin and immunoglobulin and thereby increase the diversity of the identified proteins. As a result, at least 30 new AFS proteins were identified and 44 AFS proteins were found to be differentially expressed between the DS and normal cases, where 6 of the proteins were unique to the DS cases and 11 were unique to the chromosomally normal cases. In addition, in the DS cases, 19 AFS proteins were downregulated and 8 were upregulated to varying degrees. A Western blot analysis confirmed the LC-ESI-MS/MS data, indicating that the combined detection of apolipoprotein A-II (apoA-II) and alpha-fetoprotein (AFP) could be a potential tool for diagnosing DS cases.